Born in Portland, Oregon, Rupp set junior and American high school records, while competing for Portland, Oregon's Central Catholic High School. Originally a soccer player, he caught the eye of American marathon legend Alberto Salazar, who coached him to great high school success, including two Oregon state titles in cross country (2002 and 2003) and three individual championships in track and field (1500 m in 2004 and 3000 m in 2003 and 2004). After winning the Oregon state title in cross country in 2003, he went on to finish second nationally in the 2003 Foot Locker Cross Country Championships. In the spring of 2004, Rupp won his 5000 m heat against college runners at the Stanford Cardinal Invitational with a time of 13:55.32, fourth-best in U.S. prep history. He went on to break the Oregon state records for 1500 m (3:45.3) and the mile (4:01.8), the latter mark being the eighth-best in American high school history at the time. In June 2004, Rupp broke the U.S. high school record for 3000 m with a time of 8:03.67 (since broken by German Fernandez), also breaking the high school record for 2000 m en route (5:18.5). On July 31 in Heusden-Zolder, Belgium, he broke Gerry Lindgren’s 40-year-old U.S. high school record for 5000 m by almost seven seconds, running 13:37.91 for the distance. He finished his high school career with a 10,000 m race in 29:09.56 in Brasschaat, Belgium, fourth-fastest ever for an American high schooler. He was Track and Field News "High School Athlete of the Year" in 2004.
Rupp delayed entering college, instead continuing to train and compete while coached by Salazar. He won the USA Junior Cross Country title in mid-February 2005, then placed 20th at the 2005 World Junior Cross Country Championships in France in mid-March. He then enrolled at the University of Oregon in time for the outdoor track season.
On May 7, 2005, at the Oregon Twilight Meet Rupp broke Rudy Chapa's U.S. junior (age 19 and under) record for 10,000 m with a time of 28:25.52, which is still the current North American and Pan American junior record. Two months later, he placed second in the 10,000 m at the NCAA Men's Outdoor Track and Field Championship. On July 17, 2005 Rupp broke Gerry Lindgren's U.S. junior record in the 3000 m in Lignano, Italy, with a time of 7:49.16, also the current North American and Pan American junior record.
After he led the team in the Willamette Invitational (sixth) and Pre-NCAA Invitational (12th), an injury brought Rupp's 2005 cross country season to an early end.
In indoor track, Rupp placed fifth in the 5000 m and sixth in the 3000 m at the 2006 NCAA indoor championships, earning All American status in both events. His 2006 outdoor season was brief due to the onset of hypothyroidism.
Rupp came back in 2006 to defeat two-time Pac-10 champion Robert Cheseret, Bernard Lagat's brother, of the University of Arizona to become Oregon's 10th male runner to win a Pac-10 Conference cross country title. He also led a young Oregon team to victory over the Stanford Cardinal, who had won the previous six Pac-10 titles. Rupp went on to finish sixth in the 2006 NCAA Men's Cross Country Championship.
The following March, Rupp capped his indoor season by placing third in the 5000 m and fourth in the 3000 m at the 2007 NCAA Men's Indoor Track and Field Championship. He began his outdoor season by running a 28:35 10,000 m at Stanford. During the race he caused some controversy by frequently slowing down to wait for another athlete. On April 20, 2007, Rupp made a huge comeback in the last 200 meters of a 5000 m race to edge out Chris Solinsky, improving personal best to 13:30. On April 29, 2007, Rupp defeated a stellar field to win the men's 10,000 m at the Payton Jordan Cardinal Invitational at Stanford. Rupp's time of 27:33.48 set an American-born NCAA Collegiate Record for the event and also gave him the seventh-fastest time in U.S. history. Two weeks later, Rupp won the 10,000 and 5000 m at the Pac-10 conference meet and helped Oregon to the team title. As in his freshman year, he went on to finish second in the 10,000 m at the NCAA track and field championships.
Rupp made his global senior debut at the 2007 World Championships in Athletics and he came in eleventh in the 10,000 m race.
A few months later, Rupp finished second (1 second behind the champion, Liberty's Josh McDougal) and led the Oregon Ducks to the 2007 NCAA men's cross country team championship.
Rupp redshirted the 2008 college track season to focus on the 10,000 m at the 2008 U.S. Olympic Track and Field Trials, where he finished second (27:43.11), earning a spot on the 2008 U.S. Olympic team. He went on to finish 13th in the 10,000 m at the 2008 Olympics with an American Olympic-record time of 27:36.99.
Recovering from the Olympics, Rupp avoided the early 2008 cross country season, running his first race at the Pac-10 Conference Championships, which he won in a course-record 22:55 over 8K. He then repeated as NCAA West Regional champion by running 27:41.24 to win the 10K race. In the 2008 NCAA national cross country championships, Rupp won his first individual NCAA title by outkicking Liberty University's Sam Chelanga in a time of 29:03.8, a new course record on the Terre Haute, IN, site, and leading the Ducks to repeat as NCAA team champions.
Rupp's 2009 track season was a resounding success. Indoors, he joined the sub-4:00 club for the mile on March 7 by running 3:57.86 at the Husky Last Chance Qualifier Meet in Seattle, WA. On February 13, 2009 he broke the American indoor 5000 m record with a time of 13:18.12 at the Tyson Invitational in Fayetteville, Arkansas. At the NCAA indoor nationals, he won an unprecedented triple in the 5000 m (13:41.45), the distance medley relay (running a 3:57.07 1600 m anchor leg only 90 minutes after his 5000 victory), and the 3000 m (7:48.94, the next day). This triple victory helped Oregon win its first-ever indoor national team title.
Outdoors, Rupp helped break the NCAA 4 x mile record on May 10. Rupp (3:58.93) anchored the relay, which also included his Oregon teammates Matthew Centrowitz Jr. (3:59.53), Andrew Wheating (3:59.60), and Shadrack Kiptoo-Biwott (4:05.21); they shaved a little more than a second off the old record with their time of 16:03.24. After helping Oregon defend its Pac-10 title, Rupp won the 5000 and 10,000 m at the 2009 NCAA Division I outdoor track championships. In all, Rupp earned 14 All American honors at Oregon along with five individual championships, a relay championship, two NCAA cross country team titles, and an indoor track NCAA team title.
In his last appearance for the University of Oregon, Rupp won the 10,000 m at the 2009 USA Outdoor Track & Field Championships at Hayward Field with a time of 27:52.53.
Rupp won the inaugural Bowerman Award in 2009. The Bowerman Award is given to college track's Athlete of the Year.
Having earned himself a place on the American team for the 2009 World Championships in Athletics, Rupp announced that he was turning pro, and that Michael Johnson would be his agent. At the World Championships, Rupp placed eighth, where he was one of only two non-Africans in the top 12 alongside Dathan Ritzenhein.
He then qualified for and competed at the 2010 IAAF World Indoor Championships. He set a personal best of 7:42.40 for 3000 meters, taking fifth place in the final.
Rupp knocked more than twenty seconds off his previous 10,000 m best with a run of 27:10.74 in Palo Alto at the Payton Jordan Stanford Invitational. Before that race, the American 10,000 m record was 27:13.98 by Meb Keflezighi, and though Rupp's time was over three seconds faster than that, he was beaten to the punch by Chris Solinsky, who won the race with a new American record of 26:59.60. Two months later, Rupp retained his national title in the 10,000 m with a win at the 2010 USA Outdoor Track and Field Championships. Rupp competed on the 2010 IAAF Diamond League circuit and made a series of improvements to his personal records. He broke four minutes for the mile run at the Pre Classic, running 3:57.72, set a 3000 m outdoor best of 7:43.24 at the London Grand Prix, and then improved his 5000 m time to 13:07.35 at the season-ending Weltklasse meeting.
Rupp took part in the Great Edinburgh Cross Country in 2011 and finished second behind Mo Farah, helping the American team to second place. He then took part in the New York City Half Marathon, his debut at that distance, and finished third in a time of 1:00:30, making him the third-fastest American at the distance. At the 2011 USA Outdoor Track and Field Championships he once again retained his national 10,000 m title, running the last 800 meters in a quick 1:52.59, and came back the next day to finish third in the 5000 m. Later in July, he improved his 5000 m personal best to 13:06.86 at the Diamond League meeting in Birmingham, outsprinting the reigning world cross country champion Imane Merga for second behind winner Mo Farah.
At the 2011 World Championships in Athletics Rupp finished seventh in the 10,000 m in a seasonal best of 27:26.84. He then doubled back to run the 5000 m, and though he was in the lead with Mo Farah with a little more than a lap remaining, he was outkicked and finished in ninth place with a time of 13:28.64.
Rupp finished his track season with a new American record in the 10,000 m when he ran 26:48.00 to finish third behind winner Kenenisa Bekele at the Memorial Van Damme meet on September 16, 2011. this time made Rupp the 16th-fastest performer in history at the distance.
Rupp broke Bernard Lagat's American indoor 2-mile record when he won the USATF Classic meet in a time of 8:09.72 on February 11, 2012. (Lagat reclaimed the record in 2013 at the Millrose Games in New York City.) In June, Rupp became the fifth American to break 13 minutes for 5000 m when he ran 12:58.90 at the Prefontaine Classic. He won the 10,000 m at the 2012 United States Olympic Trials in a time of 27:25.33. The run set a new Trials record, breaking Meb Keflezighi's 27:36.49 from 2004, and secured Rupp's second trip to the Olympic Games.
On June 28, 2012, Rupp broke Steve Prefontaine's last remaining record, the Olympic Trials 5000-meter record from 1972, winning the race in 13:22.67. This was a special race for Rupp, because it was his first victory over Bernard Lagat, the current U.S. 5000 m record-holder. Rupp finished the race with a superlative last lap of 52 seconds.
On August 4, 2012 at the London Olympic Games, Rupp took a surprise silver medal in the 10,000 m behind Mo Farah, his training partner, with a time of 27:30:90, after running his last lap in 53.8 seconds. This was the first time a U.S. man had medaled in the Olympic 10,000 m in 48 years, the last medal being Billy Mills's gold in the 1964 Olympics. Rupp was the only athlete in the top 10 not of East African origin. On August 8, 2012, Rupp advanced to the final of the 5000 m with a sixth-place finish in 13:17.56. On August 10, in the 5000 m Olympic final, Rupp placed seventh in 13:45.04.
On January 26, 2013, at the indoor Terrier Classic at Boston University, Rupp made an attempt to break the American indoor mile record, where he won the mile in 3:50.92, the fifth-fastest indoor mile ever run, in a field that included four other sub-four-minute performers.  Rupp's time was behind only that of Bernard Lagat among Americans. Rupp was second at the Boston Indoor Grand Prix 3000 m. On February 21, 2013 Rupp broke Lagat's national indoor record at 3000 m by more than two seconds with a time of 7:30.16 at the XL Galan meet in Stockholm, Sweden.
During the start of his 2013 outdoor season, he DNFed in the 5000 m at the Oxy High Performance Meet, but he got second in the 1500 m at this same meet in 3:36.98. He was sixth in the Prefontaine Classic 5000 m. At the 2013 USATF Championships, he won his fifth consecutive US 10k Outdoor title, in a time of 28:47.32. His teammate, Dathan Ritzenhein, led the last 4 laps or so, but he was to be outkicked by Rupp in the end. He was also the runner up in the 5000 m to Bernard Lagat, much like last year but with the opposite outcome. This qualified Rupp for two events at the IAAF World Championships in Moscow. He raced the 5000 m at the Monaco Diamond League Meet, where there were rumors of him and Lagat going after the American record in that race. However, Rupp came out on top because Lagat DNFed, no American record was broken that day. At the London Diamond League meet, his last race before Moscow, he raced in the Emsley Carr Mile, where he was the top American in an international field, even though he is a 10k specialist. He set an outdoor personal best of 3:52.11, beating out a field that included his 1500 m specialist teammate Matthew Centrowitz.
On August 10, 2013, at the 14th IAAF World Championships in Moscow, Russia, Galen Rupp placed 4th in the Men's 10,000m Final with a 27:24.39, seasonal best performance. He followed up that performance with a 13:29.87 run in the Finals of the 5000 m championship, placing 8th.
Galen Rupp set the American Indoor 5000 meter record at Boston University on January 16, 2014 in a time of 13:01.26 breaking Lopez Lomong's previous record of 13:07.00.
On January 25, Rupp set the American record in the Indoor 2 Mile with a time of 8:07.41, breaking the previous record of 8:09.49 by Bernard Lagat on February 16, 2013.
On May 30, 2014, Rupp ran a 26:44.36 at the Prefontaine Classic in the 10000 meters, breaking his own American Record of 26:48.00 set on September 16, 2011.
On June 27, 2014, Rupp won his sixth consecutive USA Outdoor Track and Field Championships 10000m run with a time of 28:12.07.
On June 10 and July 5 Galen went for the American record attempt in the outdoor 5000m. Both times he fell short due to poor pacing by the rabbits.
In its annual World Rankings issue, Track & Field News magazine recognized Rupp as the world's top athlete in the 10,000 meters for 2014, marking the first time an American runner claimed the number one position since the 1985 season.
At the 2015 USA Outdoor Track and Field Championships, Rupp won his 7th consecutive national title in the 10,000m, finishing in 28:11.61 - less than 3 seconds ahead of Ben True.
Controversy rose when Salazar was accused of providing his athletes - including Rupp - with performance-enhancing drugs. He had allegedly dosed Rupp with testosterone since the athlete was 16. As of July 2015, neither Rupp nor Salazar have faced sanctions from the World Anti-Doping Agency or the United States Anti-Doping Agency.
On 22 August 2015 at the 2015 World Championships in Athletics – Men's 10,000 metres, Galen ran with the breakaway lead pack of his training partner Mo Farah and three Kenyan athletes trying to act as a team to beat Farah. When Farah started a long kick resulting in a 54.15 last lap for the victor, the Kenyans scrambled around Rupp as they chased in vain to catch Farah. Galen was out of the picture for the last 300 metres of the race.