Seeking its seventh straight appearance in soccer's showcase, the U.S. (1-0-1) tops Group A of North and Central America and the Caribbean on goal difference over Jamaica (1-0-1), which tied 0-0 tie at Antigua and Barbuda. Guatemala (0-1-1) is last with one point.
The top two teams advance to next year's six-nation regional finals, which will produce three qualifiers for the 2014 tournament in Brazil.
The Americans extended their unbeaten streak against Guatemala to 18 games (12-0-6) since 1988 and improved to 6-0-5 against the Guatemalans in World Cup qualifying.
Dempsey scored his 27th international goal off a play that started with a short pass from Johnson on the left. Dempsey cut across to his right, talking touches as he sidestepped Carlos Gallardo and Erwin Morales, then wrong-footed Ricardo Jerez Jr. with a right-footed shot from 16 yards to the goalkeeper's right.
It was Dempsey's 28th goal of the season for club and country, including 23 for England's Fulham.
Just before the goal, Howard made a diving save on Carlos Figueroa's open 10-yard shot from an angle. Ruiz nearly tied the score in first-half injury time, hooking just wide on a left-footed shot from the top of the arc. When the second half started, Guatemala just missed with a header that went narrowly over the crossbar following a corner kick.
Johnson returned to left back after missing Friday's game because of a strained calf muscle.
U.S. coach Jurgen Klinsmann gave Geoff Cameron his World Cup qualifying debut, bringing him in to start the second half in place of Clarence Goodson, who had gotten a yellow card in the 23rd.
Real Salt Lake midfielder Kyle Beckerman entered the game in stoppage time, replacing Landon Donvovan.
U.S. 1,Guatemala 1
R Clint Dempsey scores in the 40th minute to put the U.S. ahead 1-0.
• Marco Pappa scores the equalizer in the 83rd minute for Guatemala.
• The U.S. (1-0-1) narrowly remains atop its group.