In 1987, obese, illiterate 16-year-old Claireece Precious Jones (Gabourey Sidibe) lives in the New York City ghetto of Harlem with her dysfunctional, abusive, unemployed mother, Mary (Mo'Nique), who has long subjected her to physical, mental and sexual abuse. Precious has also been raped by her father, Carl (Rodney "Bear" Jackson), resulting in two pregnancies. The family resides in a Section 8 tenement and survives on welfare. Her first child, "Mongo" (short for Mongoloid), has Down syndrome and is being cared for by Precious' grandmother, though Mary forces the family to pretend that Mongo lives with her and Precious so she can receive extra money from the government. When Precious' second pregnancy is discovered, her high school principal arranges for her to attend an alternative school, where she hopes Precious can change her life's direction. Precious finds a way out of her traumatic daily life by escaping into daydreams. In her mind, she has created an alternate world where she is loved and appreciated.
Inspired by her new teacher, Blu Rain (Paula Patton), Precious finally learns to read and write. She meets sporadically with social worker Ms. Weiss (Mariah Carey), who learns about incest in the household when Precious reveals who fathered her children. While Precious is in the hospital giving birth to her second child, Abdul, she meets John McFadden (Lenny Kravitz), a nursing assistant who shows her kindness. After her mother hits her and deliberately drops 3-day-old Abdul, Precious fights back and flees her home with Abdul. As they set out, she stops at a church window and watches the choir singing a Christmas hymn inside, imagining that she and her fantasy boyfriend are together and singing a more upbeat version of the song. Precious breaks into her school classroom because it is cold and she has nowhere to go. After Blu discovers her the next morning, she frantically calls local shelters looking for a safe place for Precious to stay. Later that night, Precious stays with Blu and her live-in partner (leading Precious to speculate that Blu is a lesbian). The next morning, Ms. Rain takes her and Abdul to find assistance for them. She tells Precious that she will be able to continue her schooling while she raises Abdul in a halfway house.
Precious's mother soon returns to inform her of her father's death from AIDS. Precious later learns that she is HIV-positive, though Abdul is not. Feeling dejected, she steals her case file from Ms. Weiss's office. As she shares the details of her file with her fellow students, she develops a new outlook on life. Later, Precious meets with her mother at the social worker's office. Ms. Weiss confronts Mary about her abuse of Precious, pointing to specific incidents going back to when Precious was 3 years old. Mary tearfully attempts to explain her lack of intervention and years of abuse, but Precious remains distant; before she leaves, she tells her mother that she won't be seeing her again. Mary begs Ms. Weiss to help her get Precious back, but a shaken Ms. Weiss silently brushes past Mary, refusing to help her because of the extent to which Precious was abused.
Now in a changed frame of mind, focused on improving life for herself and her children, Precious severs ties with her mother, takes custody of Mongo, and plans to complete a GED test to receive a high school diploma equivalency. She walks out into the city with both children in tow, ready to start a new life.