It was the final group game in round three of qualifying in the North, Central America and Caribbean zone and saw the US top their group from Jamaica.
The States were shocked by Carlos Ruiz's fifth-minute goal for Guatemala, but responded in style to lead 3-1 at the break.
Clint flicked on a corner for Carlos Bocanegra to level on 10 minutes and was then on the end of crosses from Eddie Johnson and Michael Bradley to put his team in charge.
It stayed 3-1 and USA topped the group by three points from Jamaica. The two teams now progress to the final stage of qualifying, a round-robin group of six teams where the top three will go straight to the World Cup finals in Brazil in 2014 and the team in fourth will go into an intercontinental qualifier.
The striker claimed two goals and an assist as Jurgen Klinsmann's team came from 1-0 down to beat Guatemala 3-1 in Kansas.