The fifth seed defeated Chun-Hsin Tseng 7-6(5), 7-6(1) on Tuesday night to get off the mark on the year.
"I would love to win some tennis matches in Australia. It just never happens," said Isner, who has reached the Australian Open fourth round twice. "I normally play my best at home, in the United States, and this is actually home.
"I'm a homebody and very lucky to, of course, have this tournament here in my backyard. I'm happy to move on. I've got to keep improving, and I think I can."
One year ago at the inaugural Dallas tournament, Isner reached the semi-finals but bowed out to eventual champion Reilly Opelka after a 46-point tie-break—the longest singles tie-break in ATP Tour history.
On Tuesday, the American made quick work of Tseng by comparison in the one-hour, 47-minute match. Though he could not convert on any of his five break chances in the opening set, Isner hit 22 aces and played two strong tie-breaks to win in what was just his fifth match since fracturing his left wrist at the 2022 US Open.
"He's a great player," the 37-year-old said of Tseng. "He's young, he's very fast, he's great from the back of the court, much better than I am.
"I had to use my serve to my advantage. Truthfully, the first set should have been a lot easier. I was a little bit worn out after that first set, emotionally. But I was able to stay even in second set and I played a really, really good tie-break. I'm very happy I'm not still on this court. I want to go to bed!"
Isner will face German Daniel Altmaier in the round of 16 on Thursday.