Lowry, who won the event two years ago alongside Rory McIlroy, teamed up with Koepka in the absence of the Masters champion this year.
The pair followed an opening 66 in Thursday's fourballs with a 69 in the foursomes to reach nine under at the halfway stage, one shy of the 10-under cut line.
At the top, American duo Alex Smalley and Hayden Springer held the lead at 16 under after closing their round with back-to-back birdies for a 70.
Matt Fitzpatrick and his younger brother Alex Fitzpatrick surged into a share of second after a seven-under 65 in Friday's foursomes - the lowest round of the day - cutting a six-shot overnight deficit to just one.
Victory would cap a remarkable run for Matt Fitzpatrick, who has climbed to No. 3 in the Official World Golf Rankings following wins at the Valspar Championship and the RBC Heritage, where he edged Scottie Scheffler in a play-off. Alex has also impressed this season, claiming his maiden DP World Tour title at the Hero Indian Open.
Joining the Fitzpatricks on 15 under are the teams of Davis Thompson and Austin Eckroat, along with Billy Horschel and Tom Hoge.
Elsewhere, England's Aaron Rai and American partner Sahith Theegala sit on 12 under, while Matt Wallace and Marco Penge are one shot further back at 11 under.
Matt Fitzpatrick and his younger brother Alex held their nerve down the stretch to secure a landmark win at the Zurich Classic of New Orleans, a triumph that also hands Alex a two-year PGA Tour exemption.
Bryson DeChambeau has reaffirmed his commitment to LIV Golf amid ongoing speculation about his future, saying he intends to remain with the league if it continues beyond this season.
Americans Alex Smalley and Hayden Springer lead the PGA Tour's only team event, the Zurich Classic, by one stroke.
According to a new report, Bryson DeChambeau reportedly used his time at the Masters earlier this month to explore a potential return to the PGA Tour.
