As the movie opens, a young Benjamin Franklin Gates (Hunter Gomez) is snooping around an attic when his grandfather (Christopher Plummer) catches him. Ben wants to hear the story of the gates family history, so his grandfather begins.

In 1832, Charles Carroll-the last surviving signer of the Declaration of Independence- traveled to the White House, desperate to speak with President Jackson before his death. But, since the President wasn't at the White House that night, Carroll had no choice but to share his closely-guarded secret with his stable boy- Ben's ancestor, Thomas Gates. Carroll told Gates about a fabulous treasure that had existed throughout history, collected by pharaohs and emperors for hundreds of years before being discovered by a group called the Knights Templar. The Knights believed the treasure to be too great for any one man, so they secretly smuggled it out of Europe and over to America. By the time the treasure had been taken over to America, the Revolutionary War was in full effect. The Knights had formed a secondary group called the Freemasons (and recruited members like George Washington & Benjamin Franklin) and formulated a number of secret clues and maps in a desperate attempt to keep the treasure from falling into the hands of the British. As the war ended and time went on, all of the clues were lost except one- the one belonging to Charles Carrol: "The Secret Lies With Charlotte."

Ben's father, Patrick (Jon Voight) comes in to take Ben home. He is obviously skeptical about the existence of the treasure. Ben asks if the Gates family are actually Knights. His grandfather pronounces Ben to be a Knight Templar to the family Gates.

Many years later, an adult Ben Gates (Nicholas Cage) and his team of researches are traveling across Antarctica. Fellow travelers include the financial backer Ian Howe (Sean Bean) and Ben's friend Riley Poole (Justin Bartha). The group stumbles across a figure buried in the ice. They carve it out using special tools and find the remains of a ship: the "Charlotte." Ben leads them inside, but not much can be found inside the ship. Ben finds a secret box hidden by the captain and uncovers a carved pipe. He discovers a stamp-like imprint on the pipe's base and-using his own blood- unearths a riddle: "The legend writ, the stain affected. The key in Silence undetected. Fifty-five in iron pen, Mr. Matlack can't offend."

After Ben decodes the riddle, Ian and his cronies turn on Ben & Riley and the race begins to see who can be the first to solve the mysteries and recover the hidden treasures.