A group of fish in a posh restaurant's tank swim together casually, until they look at the customers outside of the tank and see their friend Howard being eaten. This leads them to question the meaning of life. The question is explored in the first sketch, "The Miracle of Birth", which features a woman in labour being ignored by the doctors in favour of impressing the hospital's medically-clueless administrator. Meanwhile, in Yorkshire, described as "the third world", a Roman Catholic man loses his job and returns home to tell his numerous children that he will have to sell them off for scientific experiments due to the Catholic church's opposition to contraception; this leads to the musical number "Every Sperm Is Sacred". A Protestant man with his wife looks on disapprovingly, and proudly remarks that Protestants can use contraception and have sex for pleasure (though his wife points out that they never do).
In "Growth and Learning", a class of boys are taught school etiquette before partaking in a sex education lesson, which involves watching their teacher have sex with his wife. One boy laughs, and is forced into a violent rugby match pitting pupils against the adult school masters as punishment. "Fighting Each Other" focuses on three scenes concerning the British military: first, a World War I officer tries to rally his men during an attack, but they insist on presenting him with various going-away presents, including a card, a cake, and a clock; second, a modern army RSM attempts to drill his platoon, but his sarcastic remarks asking what they'd "rather be doing" ends with him actually dismissing them all to pursue leisure activities. Lastly, in 1879, during the Anglo-Zulu War, a soldier finds his leg has been bitten off. Suspecting a tiger (despite being non-native to Africa) the soldiers hunt for it and find two men suspiciously wearing two halves of a tiger costume.
The prior sequences end abruptly with a host introducing "The Middle of the Film", beginning with a surreal segment called "Find the Fish", wherein bizarre characters ask the audience to find a hidden fish over a strange musical number. "Middle Age" involves a middle-aged American couple visiting a Hawaiian restaurant with a Medieval torture theme, where, to the interest of the fish, the waiter offers a conversation about philosophy and the meaning of life. The customers are unable to make sense of it and move on to a discussion of "live organ transplants". "Live Organ Transplants" involves two paramedics visiting Mr. Brown, a card-carrying organ donor, forcefully removing his liver while he is still alive. Mrs. Brown is initially reluctant to donate her own liver while alive, but she relents after a man steps out of a fridge and sings the "Galaxy Song", discussing man's insignificance in comparison to the enormousness of the universe. The Crimson Permanent Assurance pirates from the short pre-film feature appear to invade a corporate boardroom where executives are discussing the meaning of life, but a tumbling skyscraper ends their assault.
"The Autumn Years" starts off with a musician in a French restaurant singing about the joys of having a penis. When the song is finished, the horrible, gluttonous, and grotesquely obese Mr. Creosote visits the restaurant, much to the horror of the other guests and the fish tank. He vomits continuously and devours an enormous meal. When the maître d' persuades him to eat one last wafer-thin mint, Creosote's stomach begins to rapidly expand until it explodes, spewing his chewed-up food on various diners. The maître d' then gives him the bill. Two staff members clean up Creosote's remains while discussing the meaning of life. A third waiter leads the audience to his house, spouts some weak philosophy, and then angrily dismisses them after his point trails off.
"Death" features a condemned man choosing the manner of his own execution: being chased off the Cliffs of Dover by topless women in sports gear and falling into his own grave below. In a short animated sequence, several despondent leaves commit suicide by throwing themselves from the branches of their tree. The Grim Reaper thereupon enters an isolated country house, where the hosts and dinner guests are all clueless as to who he is until the Reaper reveals his identity and tells them they all died of food poisoning from eating spoiled salmon mousse (although one guest points out she didn't eat it). They accompany the Grim Reaper to Heaven, revealed to be the Hawaiian restaurant from earlier. They enter into a Las Vegas-style hotel where it's always Christmas, with all the characters from the previous sketches as guests, and where a Tony Bennett-style singer performs "Christmas in Heaven" to the cast.
The song is cut off abruptly for "The End of the Film." An epilogue features the host of "The Middle of the Film" being handed an envelope containing the meaning of life. Pronouncing it "nothing very special," she blandly reads it out: "Try and be nice to people, avoid eating fat, read a good book every now and then, get some walking in, and try and live together in peace and harmony with people of all creeds and nations."
Graham Chapman as Chairman / Fish No. 1 / Doctor / Harry Blackitt / Wymer / Hordern / General / Coles / Narrator No. 2 / Dr Livingstone / Transvestite / Eric / Guest No. 1 / Arthur Jarrett / Geoffrey / Tony Bennett-esque singer
John Cleese as Fish No. 2 / Dr Spencer / Humphrey Williams / Sturridge / Ainsworth / Waiter / Eric's assistant / Maître D' / Grim Reaper
Terry Gilliam as Window Washer / Fish No. 4 / Walters / Middle of the Film announcer / M'Lady Joeline / Mr Brown / Howard Katzenberg
Eric Idle as Gunther / Fish No. 3 / 'Meaning of Life' singer / Mr Moore / Mrs Blackitt / Watson / Blackitt / Atkinson / Perkins / Victim #3 / Man in Front / Mrs Hendy / Man in Pink / Noël Coward / Gaston / Angela
Terry Jones as Bert / Fish No. 6 / Mum / Priest / Biggs / Sergeant / Man with Bendy Arms / Mrs. Brown / Mr Creosote / Maria / Leaf Father / Fiona Portland-Smythe
Michael Palin as Window Washer / Harry / Fish No. 5 / Mr Pycroft / Dad / Narrator No. 1 / Chaplain / Carter / Spadger / Regimental Seargeant Major / Pakenham-Walsh / Man in Rear End / Female TV Presenter / Mr Marvin Hendy / Governor / Leaf Son / Debbie Katzenberg
The main company of Monty Python members, who appeared in multiple roles in nearly every section of the film, was supported by featured cast mates:
Carol Cleveland
Simon Jones
Patricia Quinn
Judy Loe
Andrew Bicknell
Mark Holmes
Valerie Whittington
Matt Frewer
John Scott Martin