Darren Clarke’s side needed to overturn a three-point deficit in Sunday’s 12 singles matches at Hazeltine to claim an unprecedented fourth straight win in the biennial contest.
But although they won three of the first five matches convincingly, Reed edged a highly-charged opening contest with Rory McIlroy to strike a major psychological blow from which the holders never looked likely to recover.
Wins for Rickie Fowler, Brooks Koepka, Brandt Snedeker and Ryan Moore took the home side over the winning line and the final score of 17-11 was the biggest winning margin for the United States since a nine-point success at Walton Heath in 1981.
Open champion Henrik Stenson had got the first point on the board with a 3&2 win over Jordan Spieth in match two and r ookie Thomas Pieters, who had won all three of his matches alongside McIlroy, then secured his fourth point of a sensational debut with a 3&2 win over JB Holmes.
The gap was down to a single point when another rookie, Spain’s Rafa Cabrera Bello, defeated US PGA champion Jimmy Walker by the same score, only for Justin Rose to lose on the last to Fowler, who had only taken the lead for the first time in the match with a birdie on the 16th.
A miserable week for Masters champion Danny Willett, who was heckled throughout after a magazine article by his brother criticised American fans, was completed with a 5&4 defeat at the hands of rookie Koepka.
And although S ergio Garcia showed incredible nerve to follow Phil Mickelson in for a birdie on the 18th and halve their match - which featured an amazing 19 birdies - Snedeker’s win over And y Sullivan left the USA needing just half a point for victory.
The honour of securing the win fell to Moore, who was only chosen as the final wild card seven days ago after losing out in a play-off for the Tour Championship to McIlroy.
Moore was two down with three to play against Lee Westwood, who had lost his other two matches this week, but eagled the 16th, birdied the 17th and then made par on the last win to leave Westwood without a point on his 10th Ryder Cup appearance.
The victory was especially sweet for US captain Davis Love, who was also in charge when Europe came back from 10-6 down to pull off the ‘Miracle at Medinah’ in 2012.
“We have been criticised for eight to 10 years for not coming together,” Love said. “Phil Mickelson, Bubba (Watson), everyone who played on the team and who didn’t play on the team showed we all had a heart and could pull together.
“2012 was a great team and we played our hearts out but this is a different 12 and I am super proud of them. We all pulled together for this one.”
A sixth defeat in the last seven contests at Gleneagles in 2014 had prompted the formation of an 11-man ‘task force’ to examine all aspects of the US Ryder Cup process and Love added: “ We’ve been kicked around for so long and you keep losing so you feel you have to do something different.
“There was a bit of rebuilding to do and a little bit of a shift in attitude. We are not going to win every one but we are going to go into them with a better attitude.”
Clarke’s selection of Pieters proved an inspired choice, but his other wild cards - Westwood and Martin Kaymer - produced just one point from seven matches and the decision to split the successful pairing of Garcia and Cabrera Bello on Saturday proved ill-fated.
Asked if he would change any of his decisions this week, Clarke told Sky Sports: “No. I really wouldn’t. The only one I possibly may have changed was yesterday’s (afternoon) pairings, which had to be in by 11.30 and there were still matches on the course.
“I’ve had a wonderful group of vice-captains helping me every step of the way and we’ve made all our decisions together. This doesn’t happen overnight, 18 months of planning goes into it.
“I think this week the Americans have putted that much better and that makes all the difference between winning and losing.
“Congratulations to Davis (Love) and we’ll try to win it back on our own patch in two years’ time.”