The Calgary Stampeders quarterback captured the honour Thursday night at the CFL's awards banquet.
Voting was conducted by members of the Football Reporters of Canada as well as the nine CFL head coaches. A total of 60 voters participated.
It's the second outstanding player honour for Mitchell, who also won it in 2015.
Mitchell, 28, had a CFL-high - and career-best - 35 touchdown passes this season in leading Calgary to the league's best regular-season record (13-5).
The native of Katy, Tex., threw for 5,124 yards, recorded 42 completions of 30-plus yards and had a TD-to-interception ratio of 2.5, the last two being tops in the CFL.
Mitchell received 47 first-place votes to become the ninth multiple MOP winner in CFL history. He's the second-youngest to accomplish the feat as Jackie Parker won his second in 1958 at age 26.
Mitchell will lead Calgary into the Grey Cup on Sunday against the Ottawa Redblacks. It's the Stampeders' third straight championship appearance but they lost both previous times.
Hamilton Tiger-Cats quarterback Jeremiah Masoli, the CFL's second-leading passer with 5,209 yards, was the East's finalist.
Linebacker Adam Bighill of the Winnipeg Blue Bombers was named the top defensive player. The five-foot-10, 230-pound Bighill received 57 first-place votes for his second honour after winning the award in 2015 with the B.C. Lions.
Bighill, of Montesano, Wash., had 105 tackles, four sacks two interceptions and a CFL-high four forced fumbles in his first season with Winnipeg.
Bighill anchored a defence that finished tied for first in the league with 49 takeaways, second in points allowed (23.3 per game) and tied for the second-fewest yards allowed per play (6.0). The Bombers also ended the season with a turnover ratio of plus-13.
Bighill becomes the fifth Bomber to win the award and first since Jovan Johnson in 2011. He's also the ninth player to claim multiple honours.
Hamilton linebacker Larry Dean, who also recorded 105 tackles, was the finalist. The Tiger-Cats allowed the fewest offensive yards (334.3 per game) and rushing yards (110.6) in the East Division.
Ottawa players captured three honours, including two for kicker Lewis Wards (rookie, special teams). Slotback Brad Sinopoli was named the top Canadian.
Ward made 51-of-52 field goals (league-record 98.1 per cent), including a pro football-record 48 straight that will carry over into 2019. The native of Kingston, Ont., secured 50 first-place votes in rookie balloting and 43 for the special-teams honour.
Saskatchewan Roughriders receiver Jordan Williams-Lambert was the rookie finalist while B.C. Lions kicker Ty Long was the special-teams runner-up.
Sinopoli, of Peterborough, Ont., earned his second top Canadian award, first winning in 2015. The Redblacks' star had 116 catches - a single-season record for a Canadian - for 1,376 receiving yards with four TDs in helping Ottawa finish atop the East Division with an 11-7 record.
Sinopoli, who received 32 first-place votes, has broken the 1,000-yard plateau the last four straight seasons. He had a CFL-best 486 yards after the catch this year.
Winnipeg running back Andrew Harris, last year's winner and the CFL's top rusher for a second straight season, was the finalist.
Bombers tackle Stanley Bryant captured the top lineman award for the second consecutive year. He registered 44 first-place votes to become the first multiple winner since Montreal's Scott Flory (2008-09).
The six-foot-five, 311-pound Bryant led another solid season for Winnipeg's offensive line. Not only did Harris run for a league-high 1,390 yards but Bombers scored a CFL-best 53 offensive touchdowns and allowed 36 sacks, tied for third-fewest in the league.
Hamilton guard Brandon Revenberg was the finalist.
Chris Jones of the Saskatchewan Roughriders was named the CFL's coach of the year. He received 41 first-place votes.
In his third season with the Riders, Jones led the franchise to a 12-6 record and second-place finish in the West Division. That matched the most victories for the franchise since 1970 and also earned Saskatchewan its first home playoff game since 2013.
Jones becomes the fifth Saskatchewan coach to win the honour and since Corey Chamblin in 2013.
Ottawa's Rick Campbell, the 2015 winner, was the finalist.
Pierre Vercheval, a former CFL top lineman and Canadian Football Hall of Fame inductee who's now a football broadcaster, received the Commissioner's Award for outstanding contribution to Canadian football. Wally Buono, who retired as B.C. Lions head coach at season's end, was awarded the Hugh Campbell Distinguished Leadership award.
Buono, 68, capped a 46-year career as a player, coach, GM and league governor. The Canadian Football Hall of Famer and member of the Order of Canada captured a record 282 regular-season wins and won seven Grey Cups, including five as a coach.