The Blind Side is based on the remarkable true story of Baltimore Ravens' offensive left tackle Michael Oher (Quinton Aaron). Michael grew up in the inner city housing projects with his mother in Memphis, Tennessee aptly named "Hurt Village." Michael's story begins with his being homeless and coming from a broken home with a drug-addicted mother, and an absentee father. Because of his family circumstances, Family Services took control of his life as he was growing up. Unfortunately, he was being bounced around in and out of foster homes, and now as a teenager he finds himself discarded by the people he has been living with. By a stroke of luck, and the coach's wish for a player the size of Michael, he ends up being enrolled in a private Christian school where the Tuohy kids go. Michael is a quiet person. He is shown to have a kind of childlike personality, because he tries to play with kindergarten children (Rachel St. Gelais) who reject or ignore him. Michael is befriended by S.J. Tuohy (Jae Head), the youngest Tuohy, whose connection to Michael starts the ball rolling.
Mike, having no money for food, lives by scrounging half-empty containers of snacks after school games, which Mr. Tuohy notices, after which he pays for a meal ticket for the boy. One icy winter night, as Michael is walking down the road to the school gym, where he has been sleeping; Leigh Anne Tuohy (Sandra Bullock) with her husband Sean (Tim McGraw) and children JS.J. and Collins (Lily Collins), pick Michael up and take him home for the night. However, when he tries to leave in the morning, Leigh Anne insists that he stay for dinner, and the children accept Michael matter-of-factly. Soon, Leigh Anne offers him a room and bed. As she starts offering him greater and greater favours, she begins to research Michael's records, including his career aptitude test results, where the only positive score was on protective instincts. Leigh Anne will use that to explain him how to play in the field. Up to that moment, he wasn't able to get the hang of the game and its rules, and he wasn't able to understand what his role on the field was.
From that moment, Michael starts to play well and be useful to his team. At the traditional Christmas card photograph of that year, Leigh Anne invites him to appear in the family photo. Leigh Anne's friends Beth (Rhoda Griffs), Elaine (Eaddy Mays) and Sherry (Ashley LeConte Campbell) meet regularly at a local expensive restaurant. The friends laugh about Leigh Anne's "project in the projects," but she cuts them off, saying that if they don't respect what she does, she will stop seeing them.
An opportunity arises for Michael to play at university level. However, he needs his grades to improve, so the Tuohys hire a private tuition teacher, outspoken and kind Miss Sue (Kathy Bates), who is determined to succeed, because she, like Mrs. Tuohy, wants him to play for Ole Miss. During their Geography lesson, she makes a remark about University of Tennessee burying the body parts of dead people under their football field, which Michael seems to believe blindly. While he had been leaning toward Tennessee, this event decides him ultimately to sign on with Old Miss.
There comes a moment when Leigh Anne wants to have a face-to-face conversation with Michael's mother (Adriane Lenox) to enable her to adopt Michael. Although she seems unresponsive in the beginning, the mother finally wishes Michael the best. She says that social services had branded Michael "a runner," and she forecasts that Leigh Anne will find one day that he has run away for good without giving any previous notice. Leigh Anne also faces some tough guys from the projects who had made ugly insinuations about her before. They are left speechless when she threatens them and is not afraid of them at all.
Many universities want Michael to play on their teams. S.J. talks to the coaches, and leads the negotiations on Michael's behalf-- and his own. When Michael gets his grades high enough, he must make a decision, and he does. He chooses the university where Sean had played for, and where Leigh Anne had been a cheerleader. That causes Investigator Granger (Sharon Morris) to move onto the matter before Michael arrives there. She questions him as though they were holding interrogatory preceding at a police station. She thinks that the Tuohys and Miss Sue are using Michael to benefit Ole Miss, their alma mater.
Michael runs away before the interview is over, and goes to find his birth mother. The leader of the tough guys welcomes him back to Hurt Village, offers him a beer, and insinuates that Michael has had sexual relations with Leigh Anne or her daughter. This rouses Michael's protective instincts, as the gang leader threatens to go after the two ladies himself. Michael shoves him into a wall, knocking his gun aside. After thinking and questioning Leigh Ann on the matter, Michael realizes that the Tuohys are now his family, and tells Granger that that's the reason for him to choose that Ole Miss.
The film ends saying that he'll succeed and become a professional player later on. S.J in seen leading the players onto the gamefield with Michael before all local games.