The Americans took an early lead in Thursday's opening foursomes (alternate shot) at Quail Hollow and then held off a late fightback from the Internationals to triumph in four of the five matches, with Justin Thomas and Cameron Young both sinking clutch putts to secure victories.
Thomas holed a massive 27-footer on the 15th hole to give him and Jordan Spieth a 2&1 triumph over Corey Conners and Im Sung-jae.
"It was huge," Thomas said. "It was great. It was exactly what we needed kind of thing."
Young very nearly matched him with a 26-foot birdie putt on the 17th as he and Collin Morikawa beat South Koreans Lee Kyoung-hoon and Kim Joo-hyung 2&1.
"We had some matches that we played really solid and some that were really a grind," US captain Davis Love said. "A great start, a lot of heart."
The Americans have never lost a Presidents Cup on home soil, and with the disruption caused by the new LIV Golf Series hurting the Internationals even more than their US counterparts, they are strongly favoured to come out on top this week as well.
The hosts got off to the best possible start by dominating the opening match, as Xander Schauffele and Patrick Cantlay thrashed Hideki Matsuyama of Japan and Adam Scott of Australia 6&5.
"We just feel really comfortable and confident playing together," Cantlay said. "To make no bogeys it was really good golf."
All of the other matches were pretty close finishes, however, and the Internationals were able to win one of their matches, with South Korean Kim Si-woo and Australian Cameron Davis winning the last four holes to secure a 2-up victory over world number one Scottie Scheffler and Sam Burns.
But aside from their opening victory and the clutch wins secured by Thomas and Young's putts, the Love's team also won the final match of the day, a narrow 1-up victory for Tony Finau and Max Homa over Taylor Pendrith and Mito Pereira to take a formidable 4-1 lead after day one.
"We hung in there. We got off to a tough start and were behind the 8-ball early," said Internationals captain Trevor Immelman.
"We're going to have to find a way to make a few putts in the next few days. But we'll hang in there. That's what we do. We'll never quit."
"We're going to learn a lot," added Canada's Conners. "I think we're going to be just as hungry to get back out there."