[11] Sam accepted a scholarship offer from the University of Missouri (Mizzou),[12] after he was recruited by Craig Kuligowski, the team's defensive line coach.

[7][11] In his sophomore year, Sam intercepted a tipped pass in a game against the Texas Tech Red Raiders, which secured a victory to make Mizzou bowl eligible.

[16] After the season, Sam was named the SEC Co-Defensive Player of the Year, with C. J. Mosley of the University of Alabama,[17] and a first-team All-SEC selection.

[23] During his college career, Sam accumulated 123 tackles, including 36 for loss, 21 sacks, six forced fumbles and two intercepted passes.

[35][36] In a statement, President Barack Obama said that he "congratulates Michael Sam, the Rams and the NFL for taking an important step forward today in our Nation's journey" and that "[f]rom the playing field to the corporate boardroom, LGBT Americans prove every day that you should be judged by what you do and not who you are.

[42] On August 30, St. Louis released Sam as part of a final round of cuts to reduce their roster to the league-mandated 53 players before the start of the regular season.

[45] Many people believe that the decision to cut Sam from the NFL was due to the underlying issue of homophobia within American football.

[53][54][55] On May 22, 2015, Sam signed a two-year contract with Montreal Alouettes of the CFL,[56][57] which made him the first openly gay player in the league's history.

[57][58] On June 12, a day before the Alouettes' first preseason game, Sam was granted permission to leave camp for "personal reasons" to return home to Texas, and was placed on the suspended list.

[62] After leaving Montreal, Sam told radio host Dan Patrick on his show he never wanted to play in the CFL to begin with.

[64] On August 14, 2015, Sam announced, on Twitter, he was stepping away from professional football due to mental health reasons.

[69][70] On April 10, 2022, it was announced that Sam had been hired as the assistant defensive line coach for the Barcelona Dragons of the European League of Football.

[76][77] On February 25, 2024, it was announced that Sam had been hired as the assistant defensive line coach for the Panthers Wrocław of the European League of Football.

Sam often stayed with friends while in high school; the parents of a classmate gave him a bedroom in their house and had him complete household chores.

[25][79] In August 2013, Sam took the opportunity of a team introduce-yourself session to inform his Missouri teammates that he was gay, and found them supportive.

[81] The New York Times wrote that his father, a self-described "old-school ... man-and-a-woman type of guy", said "I don't want my grandkids raised in that kind of environment.

"[9] His father told the Galveston Daily News that he was "terribly misquoted", though The New York Times maintained that he was quoted "accurately and fairly.

"[82] On February 9, 2014, in an interview with Chris Connelly on ESPN's Outside the Lines,[83] Sam responded to questions about his coming-out experience and his status as one of college football's first openly self-acknowledged gay players.

[25][79] Anonymous NFL executives told Sports Illustrated they expected Sam to fall in the draft as a result of his announcement.

[84] Those statements caused National Football League Players Association executive director DeMaurice Smith to respond that any team official who anonymously downgrades Sam is "gutless".

[86] Anti-gay activist Shirley Phelps-Roper and about 15 other members of the Westboro Baptist Church, an organization widely considered a hate group, protested his appearance.

[91][92] Reported to have been dating Sam for several months, Cammisano is a fellow alum of the University of Missouri and was a member of the school's swim team.