Blake, top-seeded and ranked eighth in the world, hadn't played a singles match since losing to Rainer Schuettler in the second round at Wimbledon last month. The 78th-ranked Sela led 2-0 in the opening set and had a 30-love lead in the next game before Blake improved.
Blake took a 5-3 lead and had advantage twice with a chance to close the set, but couldn't finish. Sela won the game, then took the next two to take a 6-5 lead.
Blake tied it 6-all, then took the tiebreaker 7-2 to win the set.
"There were still some testy moments out there, especially playing a tiebreaker after you serve for a set,'' Blake said. "That can demoralize a lot of players sometimes.''
Blake said his experience allowed him to keep his early struggles in perspective. The 28-year-old won here two years ago, and has been in at least the quarterfinals in eight tournaments this season.
"You've got to put that behind you,'' he said. "There's nothing you can do to change it. When I was a kid, I probably would have whined and cried and thrown tantrums about that, but not anymore. Just put your head down and face what's in front of you. ... You can't let one point affect more than that one point.''
Sela had three aces in the first game and kept Blake off balance, but he couldn't keep it going in the second set. He kept fewer than half his first serves in play in the second set and had no aces.
"When I'm able to attack that second serve, I think that's one of the stronger parts of my game,'' Blake said. "If I can put a little pressure on that, it can affect the first serve.''
Blake struggled with his serve during the first set, but was more accurate in the second.
"I just started going for it,'' he said. "When you mis-hit sometimes, you start aiming it and it goes a little slower and it ends up not being as effective. You're not getting it where you want to.''
Blake advanced to play Woong-Sun Jun of Korea on Thursday. Kim beat Chrisa Guccione of Australia 6-4, 7-6 (4).
In the nightcap, fourth-seeded American Sam Querrey defeated Go Soeda of Japan 6-4, 6-4.
"Definitely, he's a tough player,'' Querrey said. "He's got a great backhand. It was nice (to win) considering yesterday in doubles.''
Querrey advanced to play American Vincent Spadea on Thursday. Spadea beat compatriot Donald Young 6-2, 6-4 on Tuesday.
Earlier, Rajeev Ram of the United States rallied from being down 6-3 in the tiebreaker to upset sixth-seeded Fabrice Santoro of France 7-6 (6), 6-4.
Americans Bobby Reynolds, Wayne Odesnik and John Isner, Colombia's Alejandro Falla, Germany's Tommy Haas, and South Korean Jun Woong-sun also advanced.
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