The teams of Davis Thompson-Andrew Novak, Ryan Brehm-Mark Hubbard and Aaron Rai-David Lipsky matched McIlroy and Lowry at 13-under 131 at TPC Louisiana on Friday.
They will play best ball Saturday and close with alternate shot on Sunday.
Patrick Cantlay and Xander Schauffele, the 2022 winners, were a stroke back with Callum Tarren-David Skinns, Nick Taylor-Adam Hadwin, Zach Johnson-Ryan Palmer, Luke List-Henrik Norlander and Corey Connors-Taylor Pendrith.
McIlroy and Lowry, who opened Thursday with a best-ball 61, overcame Lowry's mid-round putting woes to close with consecutive birdies. Lowry missed two short birdie putts and a makeable par putt.
"I was just trying to keep him as positive as possible and remind him that I'm here and I'm here to back him up in any way that I can," McIlroy said.
Lowry rebounded with a long par-saving putt on No.4 and blasted out of a greenside bunker to inches on No.8 after a mammoth drive by McIlroy.
"I missed a pretty short one on 18 and then another one on the second," Lowry said.
"I started to get a little bit into myself, but to roll that one in (on the fourth hole) was nice, and to play the last few holes the way we did was really nice too."
Rai and Lipsky held a one-shot lead heading into the 18th hole when Lipsky hit a wild hook that landed out of play. Lipsky was able to make a bogey putt that helped the team retain a share of the lead.
"It was nice for me to make that putt after I double-crossed that drive off the tee," Lipsky said, "That wasn't fun, I'll be honest."
Cantlay and Schauffele had the best round of the day with a 67. They were tied for the lead heading into 18th, but Cantlay's tee shot found the water, leading to a bogey.
Record crowds turned out for the first two days, which tournament officials attributed to the presence of McIlroy, the world's No.2-ranked player who has been enjoying the city's cuisine.
Earlier in the week, he admitted he was planning a quick visit to Bourbon Street in the city's iconic French Quarter, but as of Friday that had not occurred.
"Maybe this afternoon could be the time," he joked after his morning round.
Australian Harrison Endycott and partner Erik Barnes shot 73 to add to their opening 67, missing the 8-under cut by four.
