Malisse overcame the 6-foot-9 Isner's big serve, setting the tone in the third-set tiebreaker when he returned Isner's booming serve sharply for a winner.
In the midst of the fourth point of the tiebreaker, Malisse broke a string and still managed to win the point. He hit a drop shot across the net and Isner dribbled it into the net. Isner served an ace on the next point but he won only one more point the rest of the tiebreaker.
"It was close," Malisse said. "He served well just except one game at 5-2. It could have been 6-3, 6-2 if he'd kept his serve but I played well and had a a good tie breaker in the third."
Malisse served an ace at the second match point for the victory.
"It was kind of ugly out there," Isner said. "I didn't feel much pressure, I just wish I'd won."
Top-seeded Fernando Gonzalez of Chile beat qualifier Kevin Anderson of South Africa 6-4, 4-6, 6-4. Gonzalez finally got the edge when he broke Anderson in fifth game of the final set.
After Anderson went up 30-0 in the game, Gonzalez hit a forehand winner and a backhand cross-court return and Anderson followed with two errors, including a double-fault at break point.
"I think I can play better in the next round, the conditions were slow tonight," Gonzalez said. "I'm going to be better for the next match. I have to play better tennis than today.
"I don't have the good feeling of the ball. You have to keep playing and it will come."
Hewitt showed rust in a ragged first set filled with unforced errors, allowed Devvarman only two points in the second set and almost faded before finally put his younger opponent away in the tiebreaker.
"It's going to take a few weeks to get my movement back to where I want it to be," Hewitt said. "I felt going into the Australian Open I was moving as well as I ever have. So to get back to that we have a little bit of work ahead of us but we're on the right track and hopefully things continue improving."
Devvarman got into the tournament when Mardy Fish withdrew with a groin injury. He forced the third-set tiebreaker and had a 2-1 lead when Hewitt ran off six straight points and ended it at the first match point with a service winner.
Hewitt was erratic in the opening set but found his range in a 20-minute second set. He won five love games and allowed Devvarman only two points in the fourth game.
"It was hard to know what to expect," Hewitt said. "He doesn't hit a lot of winners but he gets a lot of balls back. In the second set, I served better. I tried to move him around and pick the right balls to come in on and put pressure on him.
"In the first set, I was a little bit too eager to go out and start hitting winners straight from the start.
Hewitt was leading 5-3 and serving for the match in the third set but Devvarman didn't wilt. He broke Hewitt in the ninth and 11th games and had several entertaining points.
"I think I let the match get away," Devvarman said. "He is where he is because he's been in that situation so many times, but it is disappointing to me right now.
Zeballos broke Sela in the first game of the second set and cruised the rest of the match. Sela held in the third and fifth games but won only two more points the rest of the match.
Zeballos served a love eighth game, including an ace at match point.