The sides had played to a stalemate through the first 77 minutes before Alejandro Bedoya got the ball on the wing. He crossed to Zusi, whose shot from about 12 yards beat goalkeeper DuWayne Kerr and ignited his home-team crowd of 18,467 decked out in red, white and blue.
Fans packed into Sporting Park had barely settled back down before Edgar Castillo, like Zusi a second-half substitute, found Altidore in front of an open net for another goal in the 81st minute. Altidore scored for his sixth straight international start.
The U.S. (6-2-1), which clinched its seventh straight World Cup berth last month, has 19 points in North and Central American and Caribbean qualifying and a four-point lead over second-place Costa Rica (4-2-3), which lost 1-0 at third-place Honduras (4-3-2).
Jamaica (0-5-4), whose only World Cup appearance was in 1998, was eliminated.
Zusi, who stars for Sporting KC, had entered at the start of the second half for Landon Donovan and was cheered wildly by his home fans. He returned the passion after he scored his second international goal, pumping his fist and celebrating with his teammates.
Altidore extended his own team record by scoring in his sixth straight games. The goal was his eighth of the year and his fourth in World Cup qualifiers.
It was another bitter defeat to the U.S. for Jamaica, which lost 2-1 on June 7 in Kingston when Brad Evans scored in second-half stoppage time. The Reggae Boyz fell to 1-13-8 against the U.S., including 1-5-6 in qualifiers.
Still alive at the onset - at least mathematically - Jamaica pressed the attack in the opening minutes, dominating possession and pestering goalkeeper Tim Howard.
Demar Phillips sent a free kick toward the goal that Howard got his mitts on, and Evans managed to clear it just before Darren Mattocks could get his foot on it in front of an open goal.
Jamaica had precious few decent scoring looks the rest of the night.
The U.S. won despite missing several key players due to injuries. Michael Bradley, Clint Dempsey and Fabian Johnson were unavailable, Omar Gonzalez sustained a hip strain just before he was due to join the national team, and forward Eddie Johnson strained his left groin in training Wednesday.
That gave coach Jurgen Klinsmann a chance to give several younger players a look, including Aron Johannsson, who played for Iceland's under-21 team and made his U.S. debut in August.
Evans was back after missing the Mexico match with a strained calf muscle, and Altidore, Matt Besler and Geoff Cameron were back after serving suspensions for yellow-card accumulation.
NOTES: The U.S. finished 8-0 in home qualifiers this cycle, outscoring opponents 8-0 on American soil in the hexagonal. The Americans are 25-0-2 in home qualifiers since a 2001 loss to Honduras.