Reilly has also been a member of the BC Lions, Pittsburgh Steelers, Green Bay Packers, St. Louis Rams and Seattle Seahawks.
Reilly played three seasons for Kamiakin High School in Kennewick, Washington, before relocating to Kalispell, Montana. As a senior, he set a Flathead High School record with 2,280 yards. He originally signed with NAIA Montana Tech, but chose to walk on at Central Washington.
Reilly was a co-runner-up for the Harlon Hill Trophy, which is presented to the nation’s top Division II football player, as a senior. He threw a touchdown pass in all 46 games of his college career, giving him the NCAA all-divisions record for consecutive games with a touchdown pass. This record would be tied in 2014 by Marshall's Rakeem Cato. Reilly completed 64 percent of his passes over his four years as a starter for 12,448 yards, 118 touchdowns and only 40 interceptions.
After redshirting at Washington State as a 5th-string quarterback, Reilly decided he didn't want to bide his time waiting for playing time. Central Washington offered him a chance to start right away so he transferred. He was the 2008 Great Northwest Athletic Conference Offensive Player of the Year after completing 65.2% of his passes (207 of 414) in 2008 for 3,706 passing with 37 TDs, six INTs and he rushed 103 times for 415 yards (4.0 avg.) with four touchdowns. He was also named First-team All Great NW for his efforts. He was also Third-team Little All-America.
In 2007, he started all 13 games and completed 271 of 435 passes (62.3%) for 3,386 yards, 30 touchdowns and 10 interceptions while be named Second-team All-North Central. He also rushed 129 times for 266 yards (2.1 avg.) with three touchdowns. In 2006, he started all 11 games and was 231/351 (65.8%) for 2,660 yards 21 TDs and 12 Ints., rushed 137 times for 272 yards (2.0 avg.) with four touchdowns and was named Second team All-North Central. The year prior, 2005, he started all 10 games and was 223/353 (63.2%) for 2,686 yards 30 TDs and 11 interceptions and rushed 86 times for 310 yards (3.6 avg.) with three touchdowns, while being named First-team All-Great NW.
Reilly was eligible to be selected in the 2009 NFL Draft, but went undrafted. He signed a free agent contract with the Pittsburgh Steelers. Reilly completed 10-of-15 for 117 yards during the 2009 preseason, but was waived on September 5, 2009.
On Nov. 19, 2009, Reilly was signed to the Green Bay Packers practice squad.
On December 9, 2009, he was signed off the Packers' practice squad by the St. Louis Rams. He was waived on May 4, 2010.
Reilly was claimed off waivers by the Seattle Seahawks on May 4, 2010. He was waived on May 18, 2010.
On July 26, 2010, it was announced that Reilly had signed a practice roster agreement with the BC Lions. On August 26, 2010 Reilly was activated by the Lions and spent the remainder of the year as the third-string quarterback. He dressed for all 18 games in 2011 as the third-string quarterback and shared in the Lions' 99th Grey Cup victory. He got his first pro start on October 19, 2012, against the Edmonton Eskimos due to an injury to Travis Lulay. Reilly completed 19 of 28 throwing attempts for 276 yards with two touchdowns and one interception, leading the Lions to victory of over the Edmonton Eskimos 39-19. The win clinched a first round bye for the BC Lions in the 100th Grey Cup Playoffs.
On January 31, 2013, Reilly was traded to the Edmonton Eskimos by the BC Lions; the trade included the exchange of the clubs' second round picks in the 2013 CFL Draft and the Lions receiving the Eskimos' second round pick in the 2014 CFL Draft. Entering the 2013 CFL season Reilly was in open competition with Matt Nichols for the starting quarterback job. Nichols tore his ACL in preseason which made Reilly the starting QB for the season. On August 18, 2013 (Week 8) Reilly threw for over 500 yards in a losing cause, the fourth highest performance for yards passing in a single game in the history of the Eskimos football club. In his first season as a full-time starter in the CFL Reilly threw for 4,207 yards, with 24 touchdowns and 18 interceptions. He also finished 5th in the league in rushing yards with 709. Despite his efforts the Eskimos struggled all season finishing with a record of 4-14 and missing the playoffs.
In the 2014 season, Reilly played in 15 regular season games, leading the Eskimos to the number two seed in the Western Division with a record of 12-6. After defeating the Saskatchewan Roughriders in the Western Semi-finals, Reilly and the Eskimos were defeated by the Stampeders 43-18, ending their season. It was revealed after the game that Reilly had been playing with a broken bone in his foot and had been in great pain. The injury had been caused in a previous game during the regular season.
Mike Reilly's third season in with Eskimos was once again hampered by injuries, missing 8 games. He played in the first game of the season, and the last 9; winning 8 in a row to finish the season as the first seed in the West Division. Reilly completed 214 of 329 pass attempts for 2,449 yards with 15 touchdowns and 10 interceptions (passer rating of 89.8). On November 29, 2015, the Eskimos won the 103rd Grey Cup with a score of 26-20 over the Ottawa RedBlacks in Winnipeg, Manitoba. After the game, he received the Grey Cup Most Valuable Player award after completing 21-of-35 pass attempts for 269 yards, two touchdowns and no interceptions. On April 14, 2016, the Eskimos announced they had signed Reilly to a contract extension through the 2018 CFL season. The three-year deal is reportedly worth over $400,000 in 2016 and then bumps up to over $500,000 in following seasons.