With the match locked at 4-4 in the deciding third set, Roddick elected to drop deeper behind the baseline to return the Belgian's serve. He was rewarded with a break and he then served it out to win 4-6, 6-3, 6-4.
"I wasn't returning well close in," Roddick said. "I just didn't have my timing or whatever. He missed eight of his first nine serves when I stood back and did that.
"He was in a pretty decent groove on first serves in the third set. He was hitting his spots. He has a good serve, but he doesn't normally pop aces, you know? I gave him a different look."
Roddick set up a semifinal against sixth-seeded Mardy Fish, who cruised past fellow American Taylor Dent 6-3, 6-0. Fish is targetting back-to-back titles after winning on grass a fortnight earlier in Newport, Rhode Island.
A third American, John Isner, also progressed to the semfinals, quickly escaping the breathless heat by beating Michael Russell 6-1, 6-2 in less than an hour.
Isner's semifinal opponent will be South Africa's Kevin Anderson, who defeat Slovakia's Lukas Lacko 6-3, 6-4.
Roddick improved to 9-0 on the ATP tour against Malisse, but he struggled in the first set with two double-faults and had problems throughout the match in earning just six of 38 first-return points.
However Roddick, the tour leader this year with a 28-4 record on hard courts, never lost the power of his serve and finished with 17 aces.
Malisse, the seventh seed, wasn't upset that many fans cheered after he hit errant shots.
"It's nice to have a crowd, at least," Malisse said. "Even if it's against me, it doesn't really bother me. They were really respectful."
Isner, who rose to tennis fame with a record-long match at Wimbledon, showed why he's one of the ATP tour's service leaders with 11 aces and an 89 percentage on first serves.
A brief match was exactly what he needed after laboring for more than 2-1/2 hours in the Atlanta heat against Gilles Muller on Wednesday.
"I remember just standing out there, not that I was feeling tired, it's just that sun is so intense," Isner said.
"It's brutal when you're out there and you can't get a break from the sun, you can't get a breeze out there, so it's really tough."
Isner's record five-set match at Wimbledon took three days and over 11 hours to complete. He breezed past Russell in 56 minutes.
The Isner-Anderson semifinal is a throwback to their college days, when Isner led the University of Georgia to the 2007 national title, something that made him the fan favorite at this tournament.
Isner went 3-0 against Anderson in college and is 2-1 in professional matches, including a straight-sets, second-round victory four months ago at Indian Wells.
"I'm going to have focus foremost on my serve," Isner said. That's what he's going to do, too. If it comes down to tiebreakers, so be it. If I take care of my serve, I should have a good chance to maybe win."