Ross Detwiler grew up in Wentzville, Missouri, and graduated from Wentzville Holt High School in 2004. As a senior, Detwiler helped lead Holt to its first district title in 14 years.
In college, Detwiler pitched for Missouri State University of the Missouri Valley Conference. In 2006, he was a member of the All-MVC Tournament team, and he also pitched 10 1⁄3 innings in two starts for Falmouth in the Cape Cod League, accruing a 1.74 ERA, striking out 14 batters, and issuing three walks before moving on to play for Team USA. In 2007, he finished his third year with a 2.22 ERA in 14 starts and 100 strikeouts in 89 innings.
During the summer of his freshman year in college Detwiler played for Wentzville Legion Post 323.
The Washington Nationals drafted him in the first round (sixth overall) in the 2007 Major League Baseball draft, making him the highest Missouri State draft pick in history. Detwiler was the fifth pitcher taken by the Washington Nationals/Montreal Expos franchise in the first round of the draft in the last six years following Clint Everts, Chad Cordero and Bill Bray in 2002, 2003 and 2004, respectively, and Colton Willems taken in 2006.
After being drafted and signed by the Nationals, he pitched four games in the rookie Gulf Coast League, and then five games with the high A Potomac Nationals. On September 7, 2007, he made his major-league debut, pitching one hitless inning in relief against the Atlanta Braves, striking out one. He became the first player drafted in the 2007 Draft to appear in a major-league game. He joined Cordero and Ryan Zimmerman as the third member of the Nationals franchise to be called up to the major leagues in the same year that he was drafted.
Detwiler opened the 2009 season with the Harrisburg Senators of the Class AA Eastern League. However, due to the injury of Scott Olsen, he was called up to start on May 18 against the Pirates. He went 5 innings and allowed 3 runs, striking out 6. Although he was 1–6 with a 5.00 ERA in 15 games with the Nationals in 2009, he went 1–1 with a 2.08 ERA in four September starts.
On February 18, 2010, Detwiler underwent hip surgery due to a labral tear.
Detwiler made his return to major league play in July 2011 after recovering from hip surgery, and he remained in rotation for the remainder of the 2011 season. Detwiler finished the 2011 season with a 4–5 win loss record and a 3.00 ERA.
Detwiler was named to the starting rotation for the 2012 season. Although he pitched effectively, the return of Chien-Ming Wang from injury put Detwiler in the long relief role in late May. Wang struggled in the rotation, granting Detwiler a return to the rotation a few weeks later. He was a regular starter for the rest of the year, finishing with 27 starts, plus a six-inning start, in which he allowed one unearned run, in game 4 of the 2012 NLDS.
Detwiler missed significant time in 2013 with an oblique injury and a pinched nerve in his back. He finished the year with just 71 1⁄3 innings pitched and a 4.04 ERA.
Detwiler competed in the 2013 World Baseball Classic for Team USA. He pitched four scoreless innings in relief and collected a save.
Detwiler started the 2014 season in a long relief role.
On December 12, 2014, the Nationals traded Detwiler to the Texas Rangers for Chris Bostick and Abel De Los Santos. He began the 2015 season as a starter but recorded an 0–5 record and a 6.95 ERA, before being placed on the disabled list on May 15 due to shoulder inflammation. Upon his return to the active roster, Detwiler made ten appearances out of the bullpen, and saw his ERA climb to 7.12. He was designated for assignment on July 11, 2015. He was released on July 15.
On July 17, 2015, Detwiler signed with the Atlanta Braves.
On December 22, 2015, Detwiler signed a minor league contract with the Cleveland Indians. The Indians purchased his contract on April 3, 2016. He was designated for assignment on April 29.
On July 17, 2016, Detwiler was traded to the Oakland Athletics in exchange for cash considerations, and was assigned to the Triple-A Nashville Sounds. He was called up to start against the Baltimore Orioles on August 10, when he threw 8 shutout innings for the 1–0 win. Detwiler would finish his season with 6.14 ERA. On January 18, 2017, Detwiler signed a minor league contract with the Athletics that included an invitation to spring training. He was assigned to Triple-A to begin the 2017 season, but instead opted out of his contract and elected to become a free agent before the season's start. He resigned a minor league contract a few days later and was assigned to Triple-A Nashville. Detwiler opted out of this contract on May 14, once again becoming a free agent, after having played 14 games with Nashville.
On June 6, 2017, Detwiler signed a minor league deal with the Chicago Cubs. He appeared in five games for the Triple-A Iowa Cubs before being released on July 17.
Detwiler is a sinkerballer, throwing his sinker at 90–94 mph. His other pitches are a four-seam fastball (91–95), a curveball (78–81), and a changeup (84–87). He does not usually throw the changeup to left-handed hitters or in 2-strike counts.
Detwiler has two brothers. He was a hospitality and restaurant administration major in college. As St. Louis natives, Detwiler and his family were avid fans of the Cardinals, Blues, and Rams.