Siemian was born on December 26, 1991 in Danbury, Connecticut to Walter and Colleen Siemian.
Siemian attended Olympia High School in Orlando, Florida,. On the football team, he threw for an Orange County record of 6,144 career yards and 53 touchdowns as quarterback for three seasons with the Titans. He was also an outstanding baseball shortstop, third baseman, and outfielder, and was voted Mr. Olympia by his classmates during his senior year.
After achieving a 3.9 GPA and making the National Honor Society, Siemian chose to attend Northwestern University (NU) over Rutgers, North Carolina State, and Harvard.
At Northwestern University, Siemian majored in Communication Studies and was awarded Academic All-Big Ten honors in 2013 and 2014. He redshirted during his freshman year of college in 2010.
In 2011, Siemian was a backup quarterback who played in eight games---the first against Eastern Illinois. He completed 16 of 26 passes for 256 yards and three touchdowns for the year.
In 2012, in the season-opener against Syracuse, Siemian led NU on a 75-yard game-winning drive after being down by six with 2:40 to play. Against Vanderbilt, he led back-to-back go-ahead drives in the fourth quarter, including a key 34-yard completion on a third-and-15 play. He made his first career start in a game against Indiana, throwing for 308 yards on 22-of-32 passing in a 44–29 win. He led Northwestern to a TaxSlayer.com Gator Bowl victory versus Mississippi State, where he led two touchdown drives and scored his first career rushing touchdown.
In 2013, Siemian played in all 12 games and made his second and third career starts, while playing behind "wildcat" quarterback Kain Colter. Against Illinois, he passed for 414 yards which were the 10th most ever by a Northwestern quarterback. He threw a career-most 46 times versus Minnesota, completing 25. Against Ohio State, he made a career-long pass of 67 yards. Facing Syracuse, he threw a career-high three touchdown passes. Against California, he rushed for a career-high 21 yards. For the year, he threw for 2,149 yards and 11 touchdowns. He ranked sixth in the Big Ten for completion percentage (59.7), seventh for yards per completion (12.07), and ninth in total offense (181.8).
In 2014, Siemian started the first 11 games before having a season-ending knee injury (torn anterior cruciate ligament) at Purdue on November 22. Versus Notre Dame, he passed for a season-high 284 yards and ran for a career-high 32 yards in a 43–40 overtime win. Against both Michigan and Minnesota, he posted a career-high in completions (32). Facing Penn State, he ran for a career-high three touchdowns. Versus California, he threw a 54-yard touchdown and caught a 17-yard touchdown pass. For the year, he rushed for five touchdowns and passed for 2,214 yards. The latter ranks him just outside of the top 10 in Northwestern single-season history.
Even though he started only 14 career games, Siemian completed college ranked fourth all-time at Northwestern in career passing yardage (5,931), fourth in completions (550), sixth in offensive yards (5,908) and seventh in passing touchdowns (27).
Siemian was rated the 22nd best quarterback in the 2015 NFL Draft by NFLDraftScout.com. Anticipating that he might not be drafted, Siemian lined up a job in Chicago for a career in commercial real estate. However, he was drafted with the 250th pick (overall) of the 2015 NFL Draft by the Denver Broncos. He was the seventh and final quarterback to be taken in the draft.
Siemian made his NFL debut—and only appearance of the 2015 season—against the Pittsburgh Steelers on December 20, 2015, taking a knee to close out the first half. On February 7, 2016, Siemian was part of the Broncos team that won Super Bowl 50 over the Carolina Panthers by a score of 24–10. He was inactive for the game.
In 2016, with Peyton Manning retiring and Brock Osweiler signing with the Houston Texans, it opened up a competition for the Broncos starting quarterback job between Siemian, veteran Mark Sanchez, and rookie Paxton Lynch. On August 29, Broncos head coach Gary Kubiak named Siemian the starting quarterback for the 2016 season.
Against the Carolina Panthers in the 2016 season opener and Super Bowl 50 rematch, Siemian completed 18-of-26 passes for 178 yards, one touchdown, and two interceptions in his first NFL start and victory. He was the first quarterback in NFL history to start the season opener for the defending Super Bowl champion without having thrown an NFL pass. He was the first Northwestern quarterback since Randy Dean in 1979 to start an NFL game. The following week, Siemian threw for 266 yards in a 34–20 win over the Indianapolis Colts. 215 of those yards came in the first half.
On September 25, 2016, Siemian became the first quarterback in NFL history to throw 300 yards and complete four touchdowns with no interceptions in his first career road start in a 29–17 win over the Cincinnati Bengals. His 132.1 quarterback rating was the highest achieved in the league that week. He was named the AFC Offensive Player of the Week for his performance against the Bengals.
During Week 12 in a Sunday Night Football game against the Kansas City Chiefs, Siemian threw three touchdowns with no interceptions on 20-of-34 passing for 368 yards. Although the Broncos ultimately lost in overtime, he achieved a quarterback rating of 125.6, the second best of his career to date when playing in the majority of a game.
From Weeks 8 to 14, Siemian was one of only three quarterbacks who averaged over 300 passing yards per game (the other two were Tom Brady and Kirk Cousins). By Week 16, he averaged 300.2 passing yards in his previous six games.
Although the Broncos finished the season with a 9–7 record and missed the playoffs, Siemian compiled an 18-10 touchdown-to-interception ratio and an 84.6 passer rating. On both measures, Siemian significantly outperformed the Broncos' Peyton Manning-Brock Osweiler quarterback duo of 2015.
On January 23, 2017, Siemian was named as an alternate for the 2017 Pro Bowl, but declined the invitation due to recovery from left shoulder surgery two weeks prior.
Siemian and the Broncos opened the 2017 season against the Los Angeles Chargers on Monday Night Football. Siemian completed 17-of-28 passes for 219 yards, two touchdowns and one interception as well as his first career rushing touchdown. The Broncos took a 24-7 lead, but two costly turnovers helped the Chargers make the score 24-21, but Broncos defensive end Shelby Harris blocked the Chargers attempt at a game-tying field goal, giving the Broncos the win. The following week, Siemian and the Broncos hosted the Dallas Cowboys, led by Offensive rookie of the Year Dak Prescott and 2016 leading rusher Ezekiel Elliott. The Broncos defense shut down Dallas's offense and Siemian went 22/32 for 231 yards, four touchdowns and one interception as the Broncos blew out Dallas Cowboys 42–17. For his performance, Siemian was voted the NFL's Clutch Performer of the week and the FedEx Air Player of the week.