Ben leads an expedition with Ian Howe, and his friend, Riley Poole, a computer expert, to find the Charlotte, a ship lost in the Arctic, which holds the first clue to finding the national treasure. They find a meerschaum pipe, which has a clue implying the next is on the Declaration of Independence. When Ian suggests they steal the Declaration of Independence, Ben opposes, causing a fight to ensue resulting in a massive fire fueled by gunpowder, and the group split in two. Ian and his men escape the ship while Ben and Riley take cover just before the ship explodes.
Ben and Riley return to Washington D.C. and report the potential theft of the Declaration to the FBI and Dr. Abigail Chase of the National Archives, but both dismiss their claim. Ben decides to steal the document himself from the Archives’ preservation room during a gala event. Obtaining Abigail’s fingerprints, Ben successfully obtains the Declaration but is spotted by Ian’s group just as they break in to steal it. Ben tries to leave via the gift shop but has to buy the Declaration when the clerk mistakes it for a souvenir copy; having no cash in hand at the time, Ben pays for it with a credit card. Abigail, suspecting something is astray, pursues Ben and takes back the document. Ian kidnaps her, but Ben and Riley rescue Abigail, tricking Ian by leaving behind a purchased copy of the Declaration. FBI Agent Sadusky begins tracking Ben down, using Ben's credit card information..
Unable to return home, the trio goes to Patrick’s house. Patrick tries to convince Ben that the treasure is a myth, but Ben dismisses this. The trio then study the Declaration and discover an Ottendorf cipher written in invisible ink. The message refers to the Silence Dogood letters written by Benjamin Franklin. Patrick formerly owned them but donated them to the Franklin Institute.
Using a school boy to acquire the letters’ key words, Ben, Riley, and Abigail discover a message pointing to the bell tower of Independence Hall. They find a hidden cache containing a pair of glasses with multiple coloured lenses invented by Benjamin Franklin, which, when used to read the back of the Declaration reveal a clue pointing to the symbol of Trinity Church which is located on Wall Street and Broadway in New York City.
The group is chased by Ian’s associates. Ben is arrested by the FBI, while Abigail and Riley lose the Declaration to Ian. However, Abigail convinces Ian to help them rescue Ben in exchange for the next clue. Ian agrees, arranging a meeting at the USS Intrepid where they help Ben evade the FBI.
Ian returns the Declaration and asks for the next clue, but when Ben remains coy, Ian reveals he has kidnapped Patrick as a hostage. They travel to the Trinity Church where they find an underground passage but it appears to lead to a dead end lit by a lone lantern. Patrick claims it is referencing the Midnight Ride of Paul Revere, pointing Ian to the Old North Church in Boston. Ian leaves Gates trapped in the chamber, heading for Boston. Patrick reveals the clue was a fake. They find a notch which the meerschaum pipe fits into, opening a large chamber containing the treasure. Ben contacts Sadusky, actually a Freemason, surrendering the Declaration and the treasure’s location in exchange for clemency. Ian is later arrested when Ben tips the FBI off.