The American, whose only PGA title came last March at the Puerto Rico Open, matched countryman Adam Schenk and Germany's Stephan Jaeger on five-under par 66 at Innisbrook's Copperhead course in Palm Harbor, Florida.
"We've been grinding for a little while since then to try and find some good form again," Brehm said. "It has been showing signs of good play, so we're just going to keep doing it."
Three-time major winner Jordan Spieth, the 2015 Valpsar winner, shared fourth after a bogey-free 67 with fellow Americans Maverick McNealy and 2009 US Open winner Lucas Glover.
Brehm aced the 196-yard, par-3 17th hole with a 7-iron. It was his first PGA hole-in-one and the first PGA ace at the hole since Kris Blanks in the 2012 final round.
"It kind of surprised me when I saw it go in the hole," Brehm said. "But we got a good reaction. It was a lot of fun.
"I was really just trying to cover the front edge of the green, and we had the wind that was down off of the right. We had 189 to cover the front edge and it probably flew almost 200 yards. So it was pretty fun to see that thing trickle in."
Brehm birdied all four par-5 holes and made his lone bogey at the par-4 sixth.
"We took care of the par-5s and that was nice," Brehm said. "Had a few up-and-downs and never hit one out of play. That's a recipe to just hang in there."
Jaeger, seeking his first PGA title, opened with a birdie, had bogeys at the par-3 fourth and par-4 seventh, but then birdied five of the next seven holes -- four of them on putts from inside six feet.
"I hit some good putts, drove it really nice on the back nine, gave myself a lot of chances to hit it on the greens," Jaeger said.
"These greens are pretty small, so if you've hit 'em in the right spots, you've got a lot of short putts in, and just made the right putts and scored on the par-5s."
Back-nine starter Schenk, playing for the 10th week in a row and chasing his first PGA title, sank a 51-foot birdie putt at the 18th in a run of four straight birdies that began at the 17th, the other birdie putts falling from eight feet.
After taking his lone bogey at the par-3 fourth, he sank an 11-foot birdie putt at the par-4 seventh, a 10-foot par putt at the eighth and got up and down from a bunker at nine to stay level for the lead.
GOOD FORTUNE, GOOD GOLF
"Just putted really well," Schenk said. "Fortunate on the last hole. I hit a bunker shot that hit the pin. Probably going to go eight feet by and ended up only four feet."
Schenk, playing so much before becoming a father next month, had a career best of third at the 2021 Shriners Children's Open.
Spieth, a back-nine starter, made three birdies in a row starting at the par-5 14th hole, highlighted by a birdie putt from just beyond 57 feet at the par-3 15th. He also rolled in a 31-foot birdie putt at the sixth.
"I was able to get a couple long putts to drop today to push me to 4-under, which is a really good round," Spieth said. "Playing 14 through 16 at 3-under is a really nice stretch of golf."
American Sam Burns, who opened with a 69, is trying to become the first player to win the same PGA event three consecutive years since Steve Stricker at the 2009-2011 John Deere Classic.