He ran quarterback sneaks in the short yardage offense, and scored his first CFL rushing touchdown in week 3 against the Montreal Alouettes.

In the final game of the regular season against the Edmonton Eskimos, Mitchell drove the offense downfield and gave Rene Paredes the opportunity to kick the game-winning field goal.

In the West Final vs BC, Mitchell faked a quarterback sneak on a third down gamble and threw a long pass to Maurice Price.

In the Grey Cup, with the contest out of reach, Mitchell entered the game and engineered a touchdown drive and a 2-point convert, both caught by Price.

He began the 2013 CFL season as the 3rd-string QB, and continued being the holder on field goal and convert attempts, and running quarterback sneaks in the short yardage offense.

Mitchell came on in the third-quarter after Kevin Glenn left with an injury (Drew Tate was already injured) and helped the Stamps to overcome a 24-point deficit to defeat the Alouettes on July 20, 2013.

[5] In his first CFL start, on July 26, 2013, Mitchell completed 29 of 33 attempts while passing for 376 yards, in a big win over the Winnipeg Blue Bombers.

On opening day, Bo Levi Mitchell gave the Calgary Stampeders their first win of the season 29–8 against the Montreal Alouettes.

On Thursday, July 24, 2014, Bo Levi Mitchell tied Jeff Garcia's CFL record for consecutive career winning starts, going 7–0, with a 26–22 victory over the Edmonton Eskimos.

[7] Mitchell went 12-2 as Calgary's starting quarterback, which helped the team finish first place in the CFL West Division and earn a first round playoff bye.

On November 23, 2014, in his first playoff start, Mitchell led the Stampeders to a victory in the Western Final over division rival Edmonton Eskimos, earning them a berth in the 2014 Grey Cup.

[9] In 2015, Mitchell's second full season as the Stampeders starting quarterback, he posted career highs in many passing categories, including completions, attempts, yards, and touchdowns.

[10] Mitchell and the Stampeders dismantled the BC Lions in the West Division Final, winning 42–15 and advancing to the Grey Cup in the process.

[11] He was once again the winner of the Jeff Nicklin Memorial Trophy, and prior to the Grey Cup game, was named the CFL's Most Outstanding Player for the first time.

Shortly after winning the Grey Cup Mitchell announced that he would be pursuing NFL opportunities before signing another CFL contract.

[16] Mitchell was set to become a free agent in February 2019, having decided to explore NFL opportunities before re-signing with the Calgary Stampeders organization.

[19] Mitchell also worked out for the Denver Broncos,[20] Jacksonville Jaguars,[21] Buffalo Bills,[22] New York Giants and Chicago Bears.

[23] During the 2019 CFL free agency, Mitchell officially became a free agent and had not yet been signed by an NFL team with CFL teams beginning to offer contracts such as the Toronto Argonauts, the Edmonton Eskimos and the Saskatchewan Roughriders with the minimum contract being offered to Mitchell being rumored around $750,000 per season.

[26] By mid-August Mitchell was appearing to be close to a return, however, he was placed back on the 6-game injured reserve list on August 16, 2019, after suffering a minor setback.

After having missed time with injuries during the 2019 and 2021 seasons in April 2022 Mitchell stated that "retirement might be the next step" if he is unable to maintain his health.

[33] After starting the first half of the season Mitchell was benched in Week 11 after throwing two interceptions and completing only nine passes on 16 attempts against the Toronto Argonauts.

[35] Maier continued to be the team's starting quarterback late into the season, and agreed to a contract extension, leaving Mitchell's future in Calgary in doubt.

[36] Mitchell came off the bench in the playoffs in relief of Maier, however, in the 9 minutes that he played he was unable to lead the team to victory (although surpassing Meier's passing yardage in the game) ending the Stampeders season.

On November 14, 2022, the Hamilton Tiger-Cats acquired the rights to Mitchell in exchange for two drafts picks and future considerations, with his contract set to expire in February 2023.

In total, he played and started in six regular season games where he completed 78 out of 132 pass attempts for 1,031 yards with six touchdowns and ten interceptions.

[51] Taylor Powell replaced Mitchell and threw for 319 yards and 2 touchdowns in relief, which earned him the start the following week against Edmonton.