Rory McIlroy, Graeme McDowell and Martin Kaymer all claimed victories in their respective matches to take Europe - 10-6 ahead overnight - to the brink of glory.
After Justin Rose had secured a half against Hunter Mahan to finish the week unbeaten, rookie Jamie Donaldson was the man to wipe out any hope of a United States fightback, halving the 14th hole of his clash with Keegan Bradley to remain 4up and guarantee another half-point.
Donaldson subsequently finished his match in style, firing his approach to within inches on 15 to prompt a concession from Bradley, who was beaten 4 and 3.
While the US briefly threatened to pull off a comeback to match Europe's at Medinah two years ago, the hosts were able to pick up three of the first six points.
McIlroy hit top gear to move four ahead by the turn against Rickie Fowler, before closing out a 5 and 4 win that set Europe on their way to a third consecutive triumph.
McDowell's comeback provided one of the highlights of the day and followed a period in which the USA had been on top.
Matt Kuchar, Jim Furyk and Webb Simpson all assumed the lead in their matches within a short space of time, with McDowell 3 down to Jordan Spieth.
However, improved putting helped the four-time Ryder Cup campaigner draw level through 12 and he subsequently triumphed 2 and 1.
Rookie Patrick Reed eventually got one over on the Gleneagles crowd, after plenty of exchanges and interaction, as he came through a tight battle with Henrik Stenson to prevail on the 18th.
Reed and Spieth had arguably been the star performers for the USA, with the former avoiding defeat on his first appearance at the competition.
However, European comebacks were to prove the order of the day as Paul McGinley clinched his first Ryder Cup success as a captain.
Rose eventually provided half a point, with the help of arguably the shot of the day, which saw him find the green from behind a bush on the 13th.
That put things all square in his match with Mahan, who had led by four holes, and another birdie at the last was enough to nudge Europe to the verge of victory.
Kaymer's 4 and 2 win over Bubba Watson meant Europe needed only half a point to guarantee the trophy, despite Phil Mickelson and Kuchar seeing off home favourite Stephen Gallacher and Thomas Bjorn respectively.
A hero in 2012, Kaymer chipped in from off the green to make eagle at the 16th and defeat the out-of-sorts Watson.
The German now has three Ryder Cup wins from as many appearances after Donaldson gained the half-point needed courtesy of a dominant display against Bradley.
Four up with four to play, Donaldson celebrated with a sensational approach to 15, which led to Bradley conceding and joyous celebrations from the home crowd.
With Europe's victory assured, Sergio Garcia beat Furyk for a second successive Ryder Cup to improve the hosts' advantage before Ian Poulter maintained his unbeaten singles record against Simpson.
Poulter may not have delivered a win this year but he is yet to taste defeat in Ryder Cup singles action after five matches.
Jimmy Walker's eight birdies helped him to a 3 and 2 win against Lee Westwood before rookie Victor Dubuisson was held to a half-point by Zach Johnson to round off the 140th Ryder Cup.