Davis Riley and Will Gordon grabbed a one-shot lead at the Country Club of Jackson after both firing six-under-par 66s on Thursday.
Riley, 25, completed his round without making a single bogey while Gordon, 26, had seven birdies and one bogey.
Both men are still chasing their maiden PGA Tour victories.
The duo lie one shot ahead of seven players tied for third on five under - including South African Christiaan Bezuidenhout and Belgium's Thomas Detry.
It's probably not a surprise to see Riley at the top of the leaderboard, as the world number 69 was born and raised in Mississippi and played the Country Club of Jackson course regularly as a youngster.
"I do have fond memories here individually and as a high school team we had success here," Riley said.
"It's cool coming back to a place that you have some good memories and good familiarity with."
Canada's Nick Taylor and South Korea's Kim Seong-hyeon are among a group of four players tied for 10th after shooting four-under-par 68s.
Eleven players are a further shot back on three under, three off the lead, including Brandon Wu, whose round included a hole-in-one at the par-three fourth hole.
South Africa's M.J. Daffue also made a hole-in-one en route to a two-under-par 70.