The opening scene shows the troops of Agamemnon of Mycenae ready to fight against the troops of Triopas of Thessaly. Afterwards, Prince Hector of Troy and his younger brother Paris negotiate a peace treaty with Menelaus, king of Sparta, and celebrate the end of a long and bloody war. Paris, however, is having a secret love affair with Menelaus' wife, Queen Helen, and smuggles her aboard their homebound vessel, much to Hector's fury, as this could lead to war between Troy and Greece. Upon learning of this, Menelaus meets with his elder brother, King Agamemnon of Greece, and asks his help in taking Troy. Agamemnon, who has wanted to conquer Troy for a long time, agrees, since it will give him control of the Aegean Sea. On King Nestor's advice, Agamemnon has Odysseus, King of Ithaca, persuade Achilles to join them. Achilles, who strongly dislikes Agamemnon and his ways, initially refuses, but eventually decides to go after his mother, Thetis, tells him that though he will die, he will be forever remembered.
Perseus (Sam Worthington), a son of Zeus (Liam Neeson), lives as a fisherman after the death of his wife, Io (portrayed by Gemma Arterton in the previous film), with his young son, Helius (John Bell). Zeus visits Perseus and asks for his help, saying that humans are not praying to the gods and as a result the gods are losing their power and becoming mortal. Perseus realizes the walls of Tartarus are crumbling and Zeus informs him that the imprisoned Titan Kronos will soon be free. Perseus, valuing his family's safety, refuses to get involved.
After imprisoning the Titans beneath the ocean, the Greek gods gather to Mount Olympus for Zeus, and his wife Hera have a son named Hercules. While the other gods are joyful, Zeus' jealous brother Hades plots to overthrow Zeus and rule Mount Olympus. Turning to the Fates for help, Hades learns that in eighteen years, a planetary alignment will allow Hades to locate and free the Titans to conquer Olympus, but only if Hercules does not interfere. Hades sends his minions Pain and Panic to dispose of Hercules. The two succeed at kidnapping and feeding him a formula that turns him mortal, but fail to remove his superhuman strength before Hercules is found and adopted by the farmers Amphitryon and Alcmene.
Hercules (Dwayne Johnson) is the leader of a band of mercenaries comprising the spear-wielding prophet Amphiaraus (Ian McShane) of Argos, the knife-throwing thief Autolycus (Rufus Sewell) of Sparta, the feral warrior Tydeus (Aksel Hennie) of Thebes, the Amazon archer Atalanta (Ingrid Bolsø Berdal) of Scythia and his nephew storyteller Iolaus (Reece Ritchie) of Athens. Hercules is said to be the demigod son of Zeus, who completed the legendary Twelve Labors, only to be betrayed by Hera who drove him insane and caused him to murder his wife Megara (Irina Shayk) and their children during a visit to King Eurystheus (Joseph Fiennes). Throughout the film, it is not clearly established that Hercules is truly the son of Zeus, and many are skeptical of the claim as well as of the stories of Hercules' famous Twelve Labors. Despite this, Hercules is frequently seen displaying unusual strength and nigh-unmatched skill in combat. Hercules is frequently haunted by the memory of the deaths of his wife and daughters by his hand, as well as visions of Cerberus.
In ancient times after defeating their predecessors, the Titans, the gods divided the Universe among themselves. Zeus took the skies, Poseidon took the seas, and Hades was left with the Underworld upon being tricked by Zeus. The gods created the mortals, whose faith and prayers assured the gods' immortality. As time passed, however, mortals began to question them and soon resist their creators, angering the Olympians.
Before the dawn of man or beast, immortals waged war against each other in Heaven. The victors declared themselves gods while the vanquished were renamed the Titans and imprisoned beneath Mount Tartarus. The Epirus Bow, a weapon of immense power, was lost on Earth during the war. In 1228 B.C., the mortal king Hyperion (Mickey Rourke) of Heraklion searches for the bow, intending to use it to release the Titans to get revenge on the gods for failing to save his family. Hyperion captures the virgin oracle Phaedra (Freida Pinto), believing that she can use her visions to find the Epirus Bow's resting place.
In New York City, Zeus and Poseidon meet at the top of the Empire State Building, where Zeus reveals that his master lightning bolt has been stolen and accuses Poseidon's demigod son, Percy Jackson, of the theft. Poseidon reminds him that Percy is unaware of his true identity, but Zeus declares that unless his master bolt is returned to Mount Olympus before the summer solstice, in two weeks' time, war will be waged between all the gods.
In the summer of 2006, Percy recounts the story of Thalia and her sacrifice. A young Annabeth, Luke, Grover and Thalia are running to Camp Half-Blood while being pursued by monsters. Thalia sacrifices herself to get the others into the camp, and her father Zeus transforms her into a pine tree, creating a magical border around the camp. Soon a Cyclops passes through the border and is revealed to be Tyson, Percy's half-brother. The camp is later attacked by a Colchis Bull who breaks through the border and ravages Camp Half-Blood. Percy defeats it with the help of Tyson, Annabeth, and Clarisse. Following this, Luke Castellan (who had survived his and Percy's battle in the previous film) appears and confronts Percy, trying to convert him to his cause. When Percy refuses, Luke disappears.
In Edwardian London, Professor Henry Higgins (Rex Harrison), a scholar of phonetics, believes that the accent and tone of one's voice determines a person's prospects in society. In Covent Garden one evening he boasts to a new acquaintance, Colonel Hugh Pickering (Wilfrid Hyde-White), himself an expert in phonetics, that he could teach any person to speak in a way that he could pass them off as a duke or duchess at an embassy ball. Higgins selects as an example a young flower seller, Eliza Doolittle (Audrey Hepburn), who has a strong Cockney accent. Eliza's ambition is to work in a flower shop, but her thick accent makes her unsuitable. Having come from India to meet Higgins, Pickering is invited to stay with the professor. The following morning, Eliza shows up at Higgins' home, seeking lessons. Pickering is intrigued and offers to cover all expenses if the experiment should be successful.
Three convicts, Ulysses Everett McGill (George Clooney), known as Everett, Pete Hogwallop (John Turturro) and Delmar O’Donnel (Tim Blake Nelson) escape from a chain gang and set out to retrieve the $1.2 million that Everett buried. The three get a lift from a blind man driving a handcar on a railway. He tells them that they will find a fortune, but not the one they seek. The trio make their way to Pete’s cousin Wash’s house. They remove their chains and sleep in the barn, but Wash betrays them and they are woken by policemen led by Sheriff Cooley, who have them surrounded. The police try to smoke them out, but Wash’s son rescues them.
In 1200 BC ancient Greece, King Amphitryon of Tiryns invades Argos. Amphitryon eventually fights rival King Galenus in personal combat, killing Galenus and seizing his kingdom. Queen Alcmene is disgusted by her husband's thirst for power and warmongering. She prays to Hera for guidance and Hera, wife of Zeus, tells her that she will allow Zeus to impregnate Alcemene with the savior of her people, a demi-god son to be named Hercules. The only other witness to this is Chiron, the queen's loyal adviser. Amphitryon names his new "son" Alcides, though Alcmene secretly acknowledges his true name as Hercules.
In Ancient Egypt, Ema "Emmy" Heshire (Kim Cattrall) hides in a pyramid from her mother, who wants her daughter to marry against Emmy's will. Emmy prays for the gods to get her out of the mess and to find her true love. The gods answer her prayer by making her disappear.
Eleven-year-old Kevin has a vivid imagination and is fascinated by history, particularly Ancient Greece; his parents ignore his activities, having become more obsessed with buying the latest household gadgets to keep up with their neighbours. One night, as Kevin is sleeping, an armoured knight on a horse bursts out of his wardrobe. Kevin is scared and hides as the knight rides off into a forest setting where once his bedroom wall was; when Kevin looks back out, the room is back to normal and he finds one of his photos on the wall similar to the forest he saw. The next night he prepares a satchel with supplies and a Polaroid camera, but is surprised when six dwarves spill out of the wardrobe. Kevin quickly learns the group has stolen a large, worn map, and are looking for an exit from Kevin's room before they are discovered. They find that Kevin's bedroom wall can be pushed, revealing a long hallway. Kevin is hesitant to join until the visage of a menacing head – the Supreme Being – appears behind them, demanding the return of the map. Kevin and the dwarves fall into an empty void at the end of the hallway.
King Acrisius of Argos (Donald Houston) imprisons his daughter Danaë (Vida Taylor), jealous of her beauty. When the god Zeus (Laurence Olivier) impregnates her, Acrisius sends his daughter and his newborn grandson Perseus to sea in a wooden coffin. In retribution, Zeus kills Acrisius and orders Poseidon (Jack Gwillim) to release the last of the Titans, a gigantic sea monster called the Kraken, to destroy Argos. Meanwhile, Danaë and Perseus safely float to the island of Seriphos, where Perseus grows to adulthood.
Shermer, Illinois, is a fictitious suburb of Chicago. There, nerdy social outcasts Gary Wallace (Anthony Michael Hall) and Wyatt Donnelly (Ilan Mitchell-Smith) are publicly humiliated by Ian (Robert Downey, Jr.) and Max (Robert Rusler) after they are seen swooning over two girls who happen to be their girlfriends. Dejected and disappointed at their direction in life and wanting more, Gary convinces the uptight Wyatt that they need a boost of popularity in order to get their crushes, Hilly (Judie Aronson) and Deb (Suzanne Snyder), away from Ian and Max. Alone for the weekend with Wyatt's parents gone, Gary is inspired by the 1931 classic Frankenstein to create a virtual girl using Wyatt's computer; infusing her with everything they can conceive to make the perfect dream girl. After hooking electrodes to a doll and hacking into a government computer system for more power, a power surge creates Lisa, a beautiful and intelligent woman with seemingly endless powers. Promptly, she conjures up a Cadillac convertible to take the boys out to a bar, using her powers to manipulate people into believing Gary and Wyatt are of age. The boys come up with the name Lisa (Kelly Le Brock), based upon a failed romantic experience of Gary's that ended with Lisa kicking him in the testicles.