The movie opens above the high seas with a lightning storm is brewing and raging. A group of jolly pirates are sailing on their ship, and all of them are scared of the storm. Meanwhile, the pirates' brave captain, Red Pirate Ron, who speaks in a language only understood by his parrot, warns his pirates to lower the sails.
After that, the movie continues with Tom and Jerry traveling aboard the same pirate ship. It is soon revealed that Red Pirate Ron is searching for the "Lost Treasure of the Spanish Mane." By chance, a wave carries the map to the treasure aboard. Tom hides the map, but is warned by the ghost of the Spanish Mane's captain, Don Diego de Clippershears, that if the map is not returned to the ocean by sunset, a curse will begin.
At one point, Tom and Jerry escape from a giant squid by using a cannon. The ship is then attacked by Ron's brother, Blue Pirate Bob, who also speaks with the help of his parrot (with credit for the attack due to Jerry). Bob's crew manages to steal the map, but Ron retrieves it and shoots down his brother's ship. Ron's crew celebrates and Tom is given seafood as a treat.
The sun sets and the ghost appears as a crew of skeleton pirates. Ron's crew abandons ship, and their lifeboat lands on top of the giant squid that Tom and Jerry fought earlier. Angry at Tom for not warning him about the curse, Ron expects him to row all the way to the island where the treasure is buried. Tom, however, leaves Ron's men stranded and takes only himself and Jerry to the island.
When they arrive, they meet Purple Pirate Paul, Ron and Bob's brother (who can, ironically, speak coherent English, whereas his parrot can't), who calls himself Barnacle Paul because he doesn't want be in the "color scheme name thing" his brothers are doing. He, too, is looking for the treasure, but is discouraged, having searched for over 40 years. Tom and Jerry are about to go on when Ron arrives and tells Paul that Tom has the map. Tom and Jerry run until they reach the entrance to the tomb of Don Diego.
A stone chicken guards the tomb, but Tom and Jerry defeat it. After maneuvering through many traps and tests, they reach the cave that contains the treasure. Tom rushes inside and is shocked to see the same giant squid standing guard. When it recognizes Tom, it shrieks in fear, and a stalactite crushes it. Tom and Jerry retrieve the treasure.
When Tom exits the tomb, Ron, Paul, and Bob begin to fight over the treasure. Jerry seizes this opportunity to sneak it away and onto Bob's ship, which has been fully repaired. Tom uses a palm tree to catapult himself onto the ship.
In the ship, Jerry and Spike control the ship while Tom swabs the deck.Then the ship leaves leaving Ron,Bob and Paul and their crew behind. Meanwhile, Ron, Bob, Paul and their crews remain on the island, running from the stone chicken, which somehow reassembled itself.