Victory was never in doubt after a dominant second quarter, inspired by Kevin Durant, which saw the Americans pull 23 points clear at halftime.
Durant finished with 30 points, 18 in the second quarter with four three-pointers, as the United States made it 53 straight wins in Olympic competition.
Serbia had troubled the team of NBA stars in their group-stage clash, losing 94-91 after missing a three-pointer on the buzzer, but it could not repeat that in the gold medal match.
The United States, missing such greats as LeBron James and Steph Curry, reserved its best for last, having come under criticism for previous lackluster displays.
But all that was forgotten as the Mike Krzyzewski-coached team completed the US medal tally in Rio, its 46th gold to comfortably top the table from Great Britain.
Durant, who has recently switched from Oklahoma City Thunder to NBA finalist Golden State Warriors, took the game by the scruff of the neck after an untidy first quarter.
He drained a succession of three-pointers and a spectacular dunk to settle any nerves that might have existed for the hot favorites.
Durant's teammate, Carmelo Anthony of the New York Knicks, made his own piece of Olympic history with the victory, becoming the first male basketball player to win three gold medals.
Anthony also won bronze at the 2004 Games in Athens, where the United States suffered its last defeat in Olympic competition, losing to Argentina in the semifinals.
DeMarcus Cousins added 13 points and 15 rebounds in the title match, the United States cruising to the basketball gold for the 15th time.
Spain, which restricted the United States to an 82-76 victory in the semifinals, beat Australia 89-88 in a controversial finish to the bronze medal match.
A disputed call gave Sergio Rodriguez the chance to score two from the free-throw line with five seconds remaining, as Spain trailed by a point.