Starting in a small section of the near South, both U.S. Army Captain James West and U.S. Marshal Artemus Gordon hunt for Confederate General "Bloodbath" McGrath, who is wanted for mass murder. It points back to when McGrath ordered a massacre in a settlement called New Liberty, where many of the freed slaves were murdered, including West's biological parents. The search leads to a brothel where the two try (unsuccessfully) to arrest him. It leads to a huge brawl and a cart of nytroglycerin crashing into the building that starts a fire. Both West and Gordon, the latter dressed as a woman, escape.
Five years after saving New York City from the demi-god Gozer, the Ghostbusters—Egon Spengler, Ray Stantz, Peter Venkman, and Winston Zeddemore—have gone their separate ways after having been sued by the city for property damage and barred from investigating the supernatural, forcing them out of business. Ray owns an occult bookstore and works as an unpopular children's entertainer with Winston, Egon works in a laboratory on the Columbia University campus, conducting experiments into human emotion, and Peter hosts a pseudo-psychic television show. Peter's former girlfriend Dana Barrett has had a son, Oscar, with a violinist that she married then divorced when he received an offer to join the London Symphony Orchestra. In order to take care of her baby, Dana quit her former cellist profession and now works as a restorer at the fictional Manhattan Museum of Art, working to prepare a malevolent-looking portrait of a legendary sixteenth-century tyrant named Vigo the Carpathian of Moldavia for an upcoming exhibition.
Professor Philip Brainard (Robin Williams) of Medfield College is developing a new energy source, in an attempt to raise enough money to save the college from closure. His preoccupation with his research distracts him from his fiancée, the college president Sara Jean Reynolds (Marcia Gay Harden). He has missed two weddings because of that preoccupation, much to Sara's anger. On the day of the third attempted wedding, Philip is approached by his former partner Wilson Croft (Christopher McDonald), who has profited from ideas he has stolen from the chemist and now desires to steal Sara from Philip and make her his wife, which he declares directly to Philip. Before he can make it to the wedding, his latest experiment shows fast development, forcing him to miss another wedding. The resulting substance created from the experiment is a green goo that increases in speed as it bounces and proves to be difficult to control, wreaking havoc on the neighborhood before the professor finally manages to capture it. Weebo (voiced by Jodi Benson), Philip's hovering robot assistant, classifies the substance as "flying rubber", leading Philip to christen it as "Flubber".
John Brown is a humble, but clumsy security guard working at the Bradford robotics laboratory in Riverton, Ohio, run by Artemus Bradford and his daughter Brenda, whom Brown has a crush on. Brown wishes to become a police officer, with support from his niece Penny. Brenda and Artemus create a lifelike robotic foot as part of the Gadget Program, to create cybernetically augmented police officers. Tycoon Sanford Scolex attacks the lab, steals the foot, and has Artemus murdered before escaping in his limo. Brown goes chasing him down in his car, which leads to its being destroyed by Scolex's explosive cigar leaving brown for dead, but a bowling ball coming from the fiery blast of Brown’s destroyed car smashingly crushes Scolex's hand, forcing him to replace it with a mechanical claw.
In 2286, a large cylindrical probe moves through space, sending out an indecipherable signal and disabling the power of ships it passes. As it takes up orbit around Earth, its signal disables the global power grid and generates planetary storms, creating catastrophic, sun-blocking cloud cover. Starfleet Command sends out a planetary distress call and warns starships not to approach Earth.
At Wellman College, thousands of hamsters overrun the campus, due to the massively obese, yet loving and kind-hearted, professor Sherman Klump (Eddie Murphy), who accidentally releases them due to his wide belly always accidentally hitting the button when he turns around. Meanwhile, Sherman has constructed an experimental formula that reconstructs human DNA in a way that allows them to lose weight instantaneously.
After finding success with a DNA restructuring formula in the first film, Sherman Klump has created another formula which enables those who take it to find the Fountain of Youth. He has also met and fallen in love with a colleague, Denise Gaines, who has developed a method to isolate genetic material and later becomes his fiancée. Together, their work has enabled Wellman College to receive a $150 million award from a pharmaceutical firm to the excitement of Dean Richmond. Despite his good fortune, Sherman has a major problem: the personality of his vanquished alter ego, Buddy Love, is still ingrained inside him and causes him to act out in the same crass manner Buddy does.
At a satellite base in Northern Germany, a worker named Freidrich, who is delivering secret codes finds a Cocker Spaniel puppy outside his office. He takes the puppy inside and shows it to his Bloodhound Rex. Rex senses that something is wrong with the dog and barks at it, making the worker take him outside. Both get locked out of the office. Rex looks through the window and sees the puppy taking pictures of the secret codes and revealing itself to be an evil female hairless Sphynx cat named Kitty Galore in disguise. Rex turns out to be a dog agent and reports to HQ.
The film begins with a Broadway-style number "So Long, and Thanks for All the Fish", sung by the dolphins of the world, who are aware of the Earth's impending doom. At the end, they all jump out of the oceans and into space, leaving Earth for good.
In response to a record high crime rate in Johannesburg, the South African government purchases a squadron of state-of-the-art, armour-plated attack robots from weapons manufacturer Tetravaal, developed by Deon Wilson. A competing project is the remotely controlled MOOSE, developed by soldier-turned-engineer Vincent Moore. Deon is praised for Tetravaal's success but Vincent grows jealous when the police are unwilling to give his heavy weapons platform equal attention. At home, Deon creates a prototype artificial intelligence that mimics a human mind to the point of feeling emotions and having opinions, but Tetravaal CEO Michelle Bradley refuses to let him test the A.I. on a police robot. Undeterred, Deon steals a recently damaged robot before it is destroyed and puts it in his van, along with the "guard key" needed to update the robot's software. On his way home, he is kidnapped by a group of gangsters, Ninja, Yolandi, and Amerika, who threaten to kill him unless he reprograms a police robot to fight for them. Deon installs the new software into the damaged robot, which responds with childlike terror upon powering up. Deon and Yolandi calm the robot, teaching it words and naming it "Chappie". Despite Deon wanting to stay with the robot, Ninja forces him out of their hideout.
Joanna Eberhart (Nicole Kidman) is a successful reality television executive producer. She is fired after her latest project, a show called I Can Do Better, where spouses choose between each other or prostitutes, results in one of the jilted men going on a shooting spree and attempts to assassinate Joanna, and she has a nervous breakdown. With her husband Walter (Matthew Broderick) and their two children, they move from Manhattan to Stepford, a quiet Connecticut suburb.
In Kentucky, a family watches an enormous horde of cattle running past their home, having caught fire, and a flying saucer leaving Earth. The ship explodes before it returns to Mars, and hundreds of other Martian ships leave Mars and head towards Earth.
Wayne Grey (Seann William Scott), a fireman trainee practicing in a shack in the desert near Glen Canyon, Arizona, sees a meteor strike his car and land in an underground cavern. College professor Ira Kane (David Duchovny) and his colleague, geology professor Harry Block (Orlando Jones), investigate, taking a sample of strange blue liquid that oozes from it. Ira discovers that it harbors extraterrestrial single-celled nitrogen-based organisms multiplying exponentially, condensing millions of years of evolution within a matter of hours. The next day, they take the science class to survey the meteor site and find it already surrounded by evolved oxygen-converting fungi and alien flatworms. Ira and Harry discover that the cells and organisms reproduce rapidly through mitosis after seeing one of the flatworms they collected in a jar split into another.
Graeme Willy (Simon Pegg) and Clive Gollings (Nick Frost) are British comic book enthusiasts and best friends who travel to the United States to attend the annual San Diego Comic-Con International, and to take a road trip through the American Southwest to visit sites significant to UFO lore. While driving on a remote desert highway at night, Graeme and Clive observe a car driving erratically and then crash. They stop to investigate and offer assistance to the driver, who turns out to be an alien named Paul (voiced by Seth Rogen). Clive faints, but Graeme agrees to assist Paul and gives him a ride.
Three thousand years ago, an Aztec warlord named Yaotl and his four generals discover a portal opening into a parallel universe which is said to have great power. Yaotl becomes immortal but at a high price, as his four generals were turned to stone. The portal releases thirteen immortal monsters that destroy his army as well as his enemies. In the present, the Teenage Mutant Ninja Turtles have grown apart. After defeating the Shredder, Master Splinter has sent Leonardo to Central America for training. Donatello works as an IT specialist, Michelangelo works as a birthday party entertainer called Cowabunga Carl and Raphael works at night as a vigilante nicknamed Nightwatcher. April O'Neil operates a company that locates and acquires relics for collectors with the help of her boyfriend, Casey Jones.