Southpaw Billy “The Great” Hope (Jake Gyllenhaal) is a professional boxer who competes in Light Heavyweight with an Orthodox posture, with having a record of 42W0L-0D, and is a resident of New York City together with Maureen McAdams, and their single daughter Leila (Oona Lawrence). In his fight against Darius Jones (Cedric D. Jones) at Madison Square Garden, Maureen is terrified when Billy takes several horrific hits to the face, resulting in massive bleeding out of his eye. Billy wins the fight by knockout , and retains the light heavyweight title, despite the abrasive injuries.
The media surrounds Billy the younger, upstart boxer, Miguel “Magic” Escobar ( Miguel Gomez) and taunts Billy to take on him. Maureen worries about Billy’s safety when he returns home and encourages Billy to give up. Later, Maureen speaks to Jordan Mains ( 50 Cent) who is Billy’s manager. She is not happy with Mains’ plan to have Billy accepted to sign a two-year deal for three fights.
Billy and Maureen go to a fundraiser ball , where Billy gives a speech, thanking Maureen, Leila, Jordan and his pals. Miguel is also there and, just as Billy is about to go home, Miguel insults Maureen, saying that he will take his titles away from him. This leads to an altercation. Hector’s brother Miguel fires a shot and Billy is able to hear it. Maureen is dead. Hector runs away and Maureen dies in Billy’s arms.
Billy begins to use alcohol and other substances. Billy talks to Jordan whom suggests that he sell the home in order to address his financial issues. Jordan invites Billy for a fight with Kalil Tiray. Billy is so badly beaten that his corner gives up. Blinded from headshots, Billy is able to accidentally hit the referee in his face. Billy is suspended for one year and has no income and owes the referee as well as the networks damages. His house and belongings are taken and taken away. Both Jordan and his long-time trainer Eli Frost abandon him to work with Miguel.
Billy runs his car into the tree in front of his house at night. Leila discovers the fact that Billy is bleeding on the ground and calls 911. Billy awakes at the hospital only to find out that Leila is in the care of Child Protective Services officer Angela Rivera ( Naomie Harris). There is no where else to go, Billy visits the Wills Gym where the former boxer Tick Wills ( Forest Whitaker) who is blind in one eye following his last fight ended with him injured. Tick wants to assist Billy get back on his feet. However, Tick is aware of his addiction to drugs and refuses to train him. Tick offers Billy the job of a cleaner.
Angela and Billy meet for a visit to Leila. But, Leila blames him for their problems and refuses to see him. Billy returns to the gym, and accepts the janitorial position. While at the gym he meets a young man named Hoppy ( Skylan Brooks), who is also a aspiring boxer. Tick learns from Hoppy that his father was abusive to his mother. As he starts to make amends, Billy continues visiting Leila and his determination wins her over. After winning a charity match, Billy is visited by Jordan. Miguel, the champion of Kalil Turay, is now his manager. Jordan is eager to set up the fight within six weeks as Jordan is aware that Billy isn’t going to have enough time to train. Tick says no, believing that Billy is merely seeking revenge.
Billy discovers later through Tick that Hoppy died while trying to save his mother from his father who shot him. In denial that he couldn’t help Hoppy, Tick decides to aid Billy train for the upcoming fight. The judge gives Billy custody of Leila after seeing his efforts to transform his life. Leila moves in with him. Billy visits Maureen’s grave and tells Leila that he’ll fight again. He also grants Leila the wish of her to remain with him.
In the evening of the fight, Angela brings Leila to the dressing room to can watch the fight on television. Miguel gets the early upper hand. Round after round, the fighters exchange furious punches. Miguel is then rude to Maureen which causes Billy to lose focus. Billy loses control of his temper, and almost ends the argument. Tick warns Billy to not let Miguel control him. Billy controls his anger and in the final round gets the upper hand against Miguel. In the final moments, Billy blocks a jab from Miguel and then lands a punch to the face before turning southpaw . He then, using an uncontrollable uppercut, he knocks Miguel to the floor. Miguel is able to stand up in the last minutes and both corners are occupied by the teams’ respective staffs.
Billy is named the new champion despite a split decision giving Miguel the first round. Billy falls into the corner, expressing his gratitude to Maureen and swearing his allegiance to Leila. Tick and his team raise him on their shoulders, while he shuts his eyes and smiles. After the battle, Leila meets Billy in the dressing room, and they hug for the first time since the death of Maureen. She tells Billy that Maureen would be proud, and she declares that she loves him.