Argentina handed Spain only their third defeat since 2006 after putting the reigning world and European champions to the sword early on in their friendly at the Monumental stadium in Buenos Aires.
Lionel Messi and Gonzalo Higuain, two players who ply their trade in Spain, put Argentina two up inside the opening 14 minutes and Carlos Tevez made it 3-0 in the 34th minute following a costly slip by Jose Reina.
Spain, who hit the woodwork three times in the match, pulled a late goal back through Fernando Llorente but Atletico Madrid striker Sergio Aguero made it 4-1 for the home side in injury-time.
That wrapped up the scoring and saw Argentina, under the guidance of interim boss Sergio Batista following the departure of Diego Maradona, join the United States and Switzerland as the only sides to have beaten Spain in the last 58 matches - 52 of which have seen the Iberian nation emerge victorious.
Spain boss Vicente Del Bosque made five changes to the side that started Friday's 4-0 Euro 2012 qualifying win over Liechtenstein, resting the likes of Xavi, Fernando Torres and captain Iker Casillas, and the new-look line-up soon found themselves in trouble.
Tevez gave an early warning to the visitors when he beat the offside trap to get on the end of Messi's fine through ball, but the Manchester City man dragged his shot wide of the far past with only Reina to beat.
The same two Argentinians were involved four minutes later as Spain were cut open again, but this time with a different outcome.
Tevez put Messi in inside the area and the Barcelona man coolly chipped the ball into the net as Gerard Pique and Reina closed in on the reigning FIFA World Player of the Year.
Tevez was heavily involved early on and in the 14th minute he helped make it 2-0 with a great pass for Real Madrid forward Higuain, who looked to have gone too wide as he rounded Reina but still found the net from a tight angle.
That was hardly the sort of start Spain would have been expecting but they settled down and were soon passing the ball around in trademark fashion.
Then, in the 28th minute, they came within a whisker of pulling a goal back when David Villa hit the top of the far post with a stunning 30-yard left-footed drive.
If that had gone in it would have seen Villa equal Raul's national record of 44 goals, and also given Spain a lifeline back into the match.
However, it flew away for a goal-kick and six minutes later Spain found themselves 3-0 down, and Reina nursing a very red face.
There appeared little danger as Reina collected Alvaro Arbeloa's back pass but the Liverpool goalkeeper slipped as he looked set to return possession to his team-mate and Tevez nipped in to slide the ball home.
That was a real setback for Spain just as they looked to be getting into their stride, and the European champions must have realised it was not going to be their night when Villa struck the post for a second time just before the break.
The number seven's free-kick from outside the area took a deflection off new Barca team-mate Javier Mascherano in the Argentina wall before striking the far post.
Del Bosque made four changes at the break and Spain had Argentina on the back foot for much of the second half.
Llorente went close with a header before Santi Cazorla saw his brilliant dipping volley tipped onto the bar by Sergio Romero.
Romero then palmed over a Pedro Rodriguez shot as Spain continued to push for at least a consolation goal.
That goal finally arrived in the 84th minute when Pedro fed Llorente, who turned and stabbed the ball inside the far post.
Spain had a half-chance to pull another goal back through Cazorla at the far post but Argentina survived that and then added gloss to the win when substitute Aguero headed home Gabriel Heinze's cross late on.
Argentina Spain
Lionel Messi (10) Fernando Llorente (84)
Gonzalo Higuaín (13)
Carlos Tévez (34)
Sergio Agüero (90)
http://soccernet.espn.go.com/report?id=306218&cc=4716&league=FIFA.FRIENDLY
