Sergio Garcia and Luke Donald rattled up three birdies over the front nine to go two up before the Americans hit back with consecutive birdies from the par-three 12th. Mickelson and Toms then bogeyed 15 to slip one behind.
The Europeans restored their two-hole cushion when Donald sank a curling 12-footer for birdie at the par-five 16th and victory was sealed when the teams matched pars at the 17th.
It was Garcia's eighth career win in eight Ryder Cup foursome matches and the fourth victory out of four for the Spaniard and Donald in the alternate-shot format.
Montgomerie/Westwood halved with Campbell/Taylor.
There was never more than one hole between the sides in this contest. Colin Montgomerie and Lee Westwood made the early running with birdies at the second and ninth before the Americans went ahead for the first time when their opponents bogeyed the par-five 10th.
The Europeans rallied with a birdie-two at the 12th and were back to one up after parring the 15th where Vaughn Taylor's approach found water. The Americans again levelled when their opponents bogeyed 17 and the match was halved with birdies at the last.
It was the first time Westwood had failed to win a foursomes encounter in seven matches stretching back to The Belfry in 2002.
Casey/Howell beat Cink/Johnson by 5 & 4.
Spurred on by three consecutive birdies from the par-four second, Paul Casey and David Howell raced four-up after just five holes. The next seven holes were shared before the British duo picked up their fifth shot at the par-three 12th.
Casey sealed victory in spectacular fashion at the par-three 14th, producing the fifth hole-in-one in Ryder Cup history with a four-iron from 213 yards.
Stewart Cink and Zach Johnson, who had needed to win the whole to keep the match alive, immediately conceded to give the Britons their second Cup victory together, following their fourballs win at Oakland Hills in 2004.
Harrington/McGinley lost to Furyk/Woods by 3 & 2.
Tiger Woods and Jim Furyk, playing together for the fourth successive match at the K Club, made a fast start with birdies at the third and fourth en route to a two-hole lead by the turn.
Irish duo Padraig Harrington and Paul McGinley trimmed the deficit with a birdie at the 12th before slipping back with a bogey-five at the 13th.
Furyk holed a monster putt at the 15th to put the Americans three ahead for the first time and with Woods much more solid than in the morning they sealed the win with matching pars on the next hole.
Morning fourballs:
Casey/Karlsson halved with Cink/Henry.
Casey maintained his unbeaten record in Ryder Cup fourball matches by holing a four-foot birdie putt at the final hole after the Europeans had been under pressure by a late American charge for the second day running.
A chip-in from behind the second green for a birdie-three by Robert Karlsson and an 18-foot putt by Casey at the par-three eighth helped the Europeans go two up by the turn.
Cink trimmed the deficit with a birdie at the 10th before an electric finish by rookie J.J. Henry very nearly secured a dramatic turnaround victory. He eagled the par-five 16th and birdied the 17th to put the Americans one up before narrowly missing a 10-footer to seal the win at the last.
Garcia/Olazabal beat Mickelson/DiMarco by 3 & 2.
Garcia and Jose Maria Olazabal, paired in the event for the second time, again produced sparkling golf to secure Europe's first point of the morning.
They each collected two birdies over the front nine and Olazabal picked up his third shot at the 10th for the Spaniards to go four up. Although a subdued Mickelson earned his first birdie of the round at the 14th, the Europeans were always in control and cruised to victory with two holes to spare.
Olazabal equalled Ian Woosnam's Ryder Cup record of 10-1/2 points in fourball matches while Garcia earned his fifth fourball victory in eight appearances.
Clarke/Westwood beat Woods/Furyk by 3 & 2.
With Woods badly out of form the Europeans dominated for most of the match. Westwood sank a three-footer for birdie at the first and Darren Clarke holed out from four and three feet at the fourth and fifth to put the home pair two up by the turn.
Woods, wayward off the tee for much of the round, missed several short birdie putts before finding water with his approach at the 15th. A Clarke birdie at the 11th, matched by Westwood at the 14th, lifted the Europeans to dormie four before Furyk mounted a late rearguard action when four down with four to play.
He coolly rolled in a six-footer for birdie on 15 and appeared likely to take the match to the 17th tee after picking up another shot on 16 before Clarke ended it there by chipping in from off the green.
Clarke and Westwood won their sixth Ryder Cup point together, two of them coming at the expense of Woods.
Stenson/Harrington lost to Verplank/Johnson by 2 & 1.
Rookie Johnson, playing his second match of the week, delivered a brilliant one-man show before collecting the only win of the session for the U.S.
He reeled off four birdies in the first five holes, narrowly missing a 10-footer for another, and ended the match by chipping in from off the 17th green for his seventh birdie of the round.
Wildcard pick Scott Verplank made his first appearance of the week but Johnson's performance earned an afternoon call-up ahead of his partner.