To have a chance to beat Isner, Roddick had to protect his own serve.
"I did what I was supposed to," Roddick said. "You're not going to beat John if you get broken a lot. I was able to fight off a little bit of trouble early in the first set. I just competed well tonight."
Roddick, the No. 4 seed, beat the top-seeded Isner 6-4, 6-7 (5), 6-4 in the semifinals of the Atlanta Open on Saturday night.
A victory over Muller would give Roddick his 32nd tour title and second in his past three events.
Isner was attempting to win his second straight event for the first time in his seven-year career, but he fell short in Atlanta for the third straight year. He lost to Mardy Fish in the past two Atlanta finals.
"It's pretty disappointing," Isner said. "(Fish and Roddick are) good friends of mine. It's tough. I've always wanted to win this tournament, but it just wasn't to be. There's really no shame in losing to either of those guys. That's for sure."
Roddick, who has won nine of his past 10 matches, will team up with Isner as U.S. doubles partners when the Olympics begin next week at Wimbledon.
The first set was delayed 44 minutes after Isner took a 3-2 lead. When play resumed, Roddick won four of the next five games and took the set as Isner struggled with his forehand accuracy.
Despite ending the match with 26 aces and winning 81 percent of his first-serve points, Isner was out of sync with his returns. It's a label that's stuck with Isner during his seven-year career.
The 6-foot-9 Isner matched his fastest serve of the match, at 140 mph, late in the third, but his footwork looked sluggish as he moved side to side, and his forehand kept falling wide or into the net.
"That was pretty apparent to see," Isner said. "I missed a lot of forehands. Then again, in all of my matches this tournament, I missed a lot of forehands. For me to play and do well in the tournament, I need that shot. It wasn't really there for me."
Losing a second-set tiebreaker was tough on Roddick, but he knew it would be tough to win one in the third.
That's often a big part of Isner's strategy, to get into a tiebreaker and break an opponent so that he's serving out for a set or match.
But Roddick avoided the aggravation, breaking Isner in the 10th game of the third set to close out the match.
"(Against) most people in a breaker, you can recover from losing one service point," Roddick said. "Against him, that's not necessarily the case. I'm not sure that I missed a ball besides a service return in the tiebreaker and still lost it. With his serve and weapon he has, a lot of times it's out of your control.
Muller will play for his first tour title.
At 6-foot-4, Muller had 17 aces to Soeda's two and finished the match in 1 hour, 13 minutes. Muller is 0-2 in career finals and last played for a title in 2005.
Muller advanced to the quarterfinals Thursday when Fish had to withdraw with a sprained right ankle. Fish, who was trying to win his third consecutive Atlanta title, led the match when he retired in the second set.
Against Soeda, Muller followed his usual plan for success. He had 17 aces, won 94 percent of his first serves. Among tour leaders, Muller tied for second with 79 percent of first-serve points won.
"I know if I put a high percentage of my first serve in, I'm getting a lot of free points," Muller said. "I didn't serve that well at the beginning of the week, but yesterday and today was very good."