After four years of peace talks in Cuba, President Juan Manuel Santos, 65, and rebel leader Timochenko - the nom de guerre for 57-year-old Rodrigo Londono - warmly shook hands on Colombian soil for the first time and signed the accord with a pen made from a bullet casing.
Colombians will vote on Sunday on whether to ratify the agreement, but opinion polls show it should pass easily.
The end of Latin America's longest-running war will turn the FARC guerrillas into a political party fighting at the ballot box instead of the battlefield they have occupied since 1964.
The FARC, or Revolutionary Armed Forces of Colombia, which began as a peasant revolt, must hand over their weapons to the United Nations within 180 days.
Showing its support for the peace deal, the European Union on Monday removed the FARC from its list of terrorist groups.
Kerry said Washington would also review whether to take the FARC off its terrorism list, and has pledged US$390 million for Colombia next year to support the peace process.