He played college football for the Ole Miss Rebels, earning unanimous All-American honors as a senior in 2008.

His mother suffered from alcoholism and crack cocaine addiction, and his father, Michael Jerome Williams, was frequently in prison.

He applied for admission to Briarcrest Christian School at the suggestion of Tony Henderson, an auto mechanic with whom he was living temporarily.

In 2004, Leigh Anne and Sean Tuohy, a couple with a daughter and son attending Briarcrest, invited Oher to live with them.

He averaged 22 points and 10 rebounds per game, earning All-State honors by helping lead the basketball team to a 27–6 record and winning the district championship in Oher's senior year.

Taking and passing the online courses allowed him to replace D's and F's earned in earlier school classes, such as English, with A's,[8] raising his graduating GPA above the required minimum.

Though he received scholarship offers from Tennessee, LSU, Alabama, Auburn, and South Carolina, Oher ultimately decided to play for Ed Orgeron at the University of Mississippi, the alma mater of his guardians, Leigh Anne and Sean Tuohy.

[9] His decision to play for the Ole Miss Rebels football team sparked an investigation by the National Collegiate Athletic Association (NCAA).

The first issue was that Oher's grade-point average (GPA) was still too low to meet the requirements for a Division I scholarship at the time of the offer from Ole Miss.

[2] The second issue was the Tuohys' preexisting relationship with the school and the fact that Ole Miss hired Freeze twenty days after Oher signed his letter of intent.

Freeze was found guilty of secondary violations for contacting other Memphis-area recruits before joining the Ole Miss staff.

[2][10] Oher started in ten games as a guard during his first season with the Ole Miss Rebels, becoming a first-team freshman All-American.

He was academically successful at Ole Miss, and his tested IQ score increased 20–30 points between when he was measured in the public-school systems and in college.

He played right tackle in his first post-season game, January 10, 2010, against the New England Patriots, and did not allow a single sack as the Ravens won 33–14.

[43] In August 2023, Oher filed a lawsuit alleging that Leigh Ann and Sean Tuohy never actually adopted him, but instead created a conservatorship that granted them legal authority to make business deals in his name.

He alleged that the Tuohys used their power as conservators to strike a deal that paid them and their two children millions of dollars in royalties from The Blind Side movie while Oher got nothing.

[44][45] Oher's legal action asked the court to end the Tuohys' conservatorship and issue an injunction barring them from using his name and likeness.

It also asked for a full accounting of the money the Tuohys earned using Oher's name, to be paid his share of profits, and other compensatory and punitive damages.

[6] The Tuohy family later claimed in legal documents Oher tried to extort $15 million from them or else he would take his accusations to the press and social media.