The Sahara desert near the Tozeur oasis in Tunisia was the location of the Tanis dig site in the film. In January 1978, Lucas, Kasdan, and Spielberg spent about nine hours a day over three to five days at Lucas' assistant's house in Sherman Oaks, Los Angeles, developing Lucas' outline.

The film spent most of the following nine weeks as the number one film, and forty-weeks straight as one of the top ten highest-grossing films. The film was nominated for several awards, and won five Academy Awards, seven Saturn Awards, and one BAFTA, among other accolades. Jones' attire—a leather jacket and khaki pants—was based on Humphrey Bogart's in The Treasure of the Sierra Madre (1948) and Charlton Heston in Secret of the Incas (1954). Hunter believed this focus on masculinity was short-sighted, and these films succeeded because they offered escapism from reality, and presented an outclassed hero who reflected the audiences' own feelings of powerlessness.According to Steven Spielberg, Marion was set to appear in the prequel Indiana Jones and the Temple of Doom, alongside her father Abner, but George Lucas scrapped the idea. In his haste, he forgot to mind the wall trap he had witnessed Indy test and is killed; Indiana makes it out. It is considered a touchstone of modern cinema, creating a film framework still emulated by other films.

Filming took place on sets at Elstree Studios, England, and on location mainly in La Rochelle, France, Tunisia, and Hawaii. Other changes included the addition of a scene where the Ark makes a humming noise in the Bantu Wind hold and the removal of a scene showing Jones holding on to the U-boat periscope to follow the Nazis; Spielberg thought it looked poor and hoped the audiences would not care how Jones accomplished the feat.

Pre-release polling showed little audience interest in the film leading up to its June 12, 1981, release date, especially compared to Superman II.