The film stars Bill Murray as Steve Zissou, an eccentric oceanographer who sets out with his crew to exact revenge on the "jaguar shark" that ate his partner Esteban.

The film also features Owen Wilson, Cate Blanchett, Willem Dafoe, Michael Gambon, Jeff Goldblum, Anjelica Huston, and Bud Cort.

The crew aboard Zissou's aging research vessel Belafonte includes his estranged wife Eleanor, chief strategist and financial backer; Pelé dos Santos, a safety expert and Brazilian guitarist who sings David Bowie songs in Portuguese; and Klaus Daimler, the German first mate who views Zissou and Esteban as father figures.

Other crew members include Vikram Ray, cameraman; Bobby Ogata, frogman; Vladimir Wolodarsky, physicist and soundtrack composer; Renzo Pietro, sound man; and Anne-Marie Sakowitz, a script girl.

After they meet at Zissou's latest premiere, Ned takes annual leave from his job as an airline pilot in Kentucky to join his crew.

On their mission to find the jaguar shark, the Belafonte steals tracking equipment from a remote station owned by more successful oceanographer (also Eleanor's ex-husband and Zissou's nemesis), Alistair Hennessey.

They then sail into unprotected waters and are attacked by Filipino pirates, who steal Ned's money and kidnap Bill Ubell, "a bond company stooge" assigned to the project.

[9] Writing about the metaphorical aspects of the film's setting—somewhere in the Mediterranean—film critic Elena Past says that the underwater scenes, because they are central to the storyline, make The Life Aquatic similar in some ways to Respiro.

[11] In addition to the luminescent-spotted jaguar shark, other fictional lifeforms (some stop-motion-animated) are cited and appear throughout the film, such as the rhinestone bluefin, crayon ponyfish, wild snow-mongoose, electric jellyfish, and sugar crabs.

The film also features many rock songs from the 1960s-1980s, and several instrumental pieces composed by Sven Libaek for the underwater documentary television series Inner Space.

Additionally, the film and soundtrack feature Seu Jorge performing David Bowie songs in Portuguese on the acoustic guitar.

The film has a 57% approval rating on Rotten Tomatoes, based on 226 reviews, with an average rating of 6.10/10; the website's consensus states: "Much like the titular oceanographer, The Life Aquatic with Steve Zissou's overt irony may come off as smug and artificial – but for fans of Wes Anderson's unique brand of whimsy, it might be worth the dive.

He also criticized the film's deliberately "weird" set ups, which leave the viewer with "the impression of having nearly drowned in some secret and melancholy game.