Starry-eyed Esther Blodgett (Judy Garland) comes to Hollywood hoping to break into the movies. Her prayers seem to be answered when leading Hollywood actor, Norman Maine (James Mason), catches her eye and turns her into the famous actress Vicki Lester. Norman and Vicki marry, but it soon becomes apparent that Norman is an alcoholic and that it's up to Vicki to support him.

A Star Is Born is a remake of A Star Is Born (1937), which was based on a story by William A. Wellman and Robert Carson and a screenplay by Dorothy Parker and Alan Campbell who, in turn, based on a previous film in 1932. The 1932 film's original title was The Truth About Hollywood based on a story by Adela Rogers St. Johns. St. Johns loosely based her plot on the experiences of actress Colleen Moore and her husband, alcoholic producer John McCormick (1893-1961), and the life and death of director Tom Forman, who committed suicide following a nervous breakdown. Another remake, also titled A Star Is Born (1976), was released in 1976, and yet another A Star Is Born (2018) was released in 2018.

As read by the justice of the peace when he marries Norman and Vicki, Norman's real name is Ernest Sidney Gubbens.

A Star is Born was restored in 1983 to its original running time. The original (1954) release premiered at 181 minutes, but theatre owners complained about the length, wanting a shorter film so they could have more showings per day, hence more money in the box office. Consequently, Warner Bros shortened it, cutting out 27 extra minutes. The excised footage was then carelessly handled, lost, or not filed properly. After an extensive search, about 20 minutes of actual film and the original soundtrack were found and re-added to the 154 minute film. Where film footage was not able to be restored, production stills were inserted. The missing seven minutes of footage has never been found. The whole story on what happened to the lost footage can be read here.

After being released to his wife following his arrest for drunkenness, Norman and Vicki go home. As Norman is lying in bed, he overhears Vicki telling Oliver (Charles Bickford) that she's decided to retire from the screen in order to tend to her husband. Later, Norman announces that he's going for a swim in the ocean. It's his new dedication to becoming fit again, he says. His body is found a few days later. Newspaper reports say he died from accidental drowning. Vicki goes deeply into mourning, such that she screams following the attention paid to her at Norman's funeral. In the final scene, Vicki attends a benefit where she sees the heart that Norman drew on the wall with their initials in it. When asked to make a speech, she starts it out by saying, "This is Mrs Norman Maine!" The crowd roars.