Born Michael Jerome Williams, Jr., in Memphis, Tennessee, he was one of 12 children born to Denise Oher. His mother was an alcoholic and crack cocaine addict, and his father, Michael Jerome Williams, was frequently in prison. Due to his upbringing, he received little attention and discipline during his childhood. He repeated both first and second grades, and attended eleven different schools during his first nine years as a student. He was placed in foster care at age seven, and alternated between living in various foster homes and periods of homelessness. Oher's biological father was a former cell mate of Denise Oher's brother and was murdered in prison when Oher was a senior in high school.
Oher played football during his freshman year at a public high school in Memphis and applied for admission to Briarcrest Christian School at the instigation of acquaintance Tony Henderson, an auto mechanic, with whom he was living temporarily. Henderson was enrolling his son at the school in order to fulfill the dying wish of the boy's grandmother and thought Oher might enroll as well. The school's football coach submitted Oher's school application to the headmaster, who agreed to accept him if Oher could complete a home study program first. Despite not finishing the program, he was admitted when the headmaster realized that his requirement had removed Oher from the public education system.
After the 2003 football season at Briarcrest, he was named Division II (2A) Lineman of the Year in 2003, and First Team Tennessee All-State. Scout.com rated Oher a five-star recruit and the No. 5 offensive lineman prospect in the country. Before that season and for his prior 20 months at Briarcrest, Oher had been living with several foster families. In 2004, Leigh Anne and Sean Tuohy, a couple with a daughter and son attending Briarcrest, allowed Oher to live with them and eventually adopted him. The family began tending to his needs after becoming familiar with his difficult childhood. They also hired a tutor for him, who worked with him for 20 hours per week.
Oher also earned two letters each in track and basketball. He averaged 22 points and 10 rebounds a game, earning All-State honors by helping lead the basketball team to a 27–6 record, winning the district championship as a senior. Oher was also a state runner-up in the discus as a senior.
Oher eventually increased his 0.76 grade point average (GPA) to a 2.52 GPA by the end of his senior year so he could attend a Div. I school by enrolling in some 10-day-long internet-based courses from Brigham Young University. Taking and passing the internet courses allowed him to replace Ds and Fs earned in earlier school classes, such as English, with As earned via the internet. This finally raised his graduating GPA over the required minimum.
Though he received scholarship offers from Tennessee, LSU, Alabama, Auburn and South Carolina, Oher ultimately decided to play for Coach Ed Orgeron at the University of Mississippi, alma mater of his guardians, Leigh Anne and Sean Tuohy. His decision to play for the Ole Miss Rebels football team sparked an investigation by the 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. That difficulty was corrected by graduation, when Oher completed online classes through Brigham Young University.
The second issue was the Tuohys' preexisting relationship with the school and the fact that Oher's high school coach, Hugh Freeze, was employed by Ole Miss twenty days after Oher signed his letter of intent. Freeze asserted that his position with Ole Miss was not an example of quid pro quo for encouraging Oher to attend the school, but rather the result of his preexisting relationship with Ole Miss offensive coordinator Noel Mazzone. The NCAA did not close its case on its