The 14-time major champion Tiger Woods suffered only his second singles defeat.
Italy's Francesco Molinari became the first European and only the fourth player ever to go 5-for-5 in a Ryder Cup.
After a 4 and 3 win over Tiger Woods and Patrick Reed in the morning fourballs, Tommy Fleetwood and Francesco Molinari thumped the 14-time major champion and Bryson DeChambeau 5 and 4 in the foursomes.
The Americans swept the first three matches in Friday's fourballs before Fleetwood and Molinari fought back.
Fourteen-time major champion, Tiger Woods will draw much of the attention as he plays his first Ryder Cup since 2012.
Tiger Woods, 14-time major winner, carded a one-over-par 71 at Atlanta's East Lake Golf Course to claim the 80th PGA Tour title of his glittering career.
A Tiger Woods victory would be an 80th PGA Tour triumph and take him to within two wins of Sam Snead's all-time 82 Tour victories.
This will be only the second time that the Ryder Cup is staged outside of Britain and Ireland after Spain's Valderrama in 1997.
Tiger Woods was named to the United States' Ryder Cup team on Tuesday as captain Jim Furyk also added veteran Phil Mickelson and in-form Bryson DeChambeau to his line-up.
Tiger Woods proved at Bellerive Country Club that he is back and a force to be reckoned with once again.
Tiger Woods returns to the scene of his most recent victory when he tackles the WGC Bridgestone in Akron, Ohio, just making the elite field a testament to the superstar's resilience.
Jordan Spieth shot a superb six-under-par 65 in benign conditions on Saturday to catapult himself up the leaderboard.
Tommy Fleetwood is dreaming of becoming the first English golfer to lift the Claret Jug since Nick Faldo in 1992.
Woods ended the round equal second with fellow American Brandt Snedeker (67) and Englishman Justin Rose (66), with Canadian surprise package Conners continuing to lead, the PGA Tour rookie posting a 68 for a nine-under 204 total.
Sixteen-time Grand Slam champion Nadal, while holidaying in the Bahamas, turned up at the Albany Golf Course to watch Woods in action.
Tiger Woods birdied on holes 3, 8, 10, 13, 14 but lost the advantage with bogeys on the par-five 9 and 15.
Woods, who has undergone multiple back surgeries in his long and illustrious career, is set for his latest comeback at this week's Hero World Challenge.