Coach Laurent Blanc fielded two right-backs with Anthony Reveillere in the defensive position and Mathieu Debuchy higher up the pitch to contain the threat of Andres Iniesta and Jordi Alba.
But Iniesta broke down the wing to feed Alba and Xabi Alonso ran on to his cross to open the scoring with a downward header in the 19th minute.
Alonso completed Spain's 2-0 win with a stoppage-time penalty.
"The plan was to reach half-time at 0-0," Blanc told a news conference.
"We had analysed the Spanish line-up well because they had two very strong players on the left but what is the most frustrating thing is that we conceded the goal from that side," he added.
France were left chasing ghosts for the remainder of the game and failed to turn their very few chances into goals.
"What I regret is that we conceded the goal early in the game," said Blanc.
"But let's be realistic, Spain are a better team and tonight's game proved it once again."
Blanc, however, waited until after the hour to make his substitutions, with Samir Nasri and Jeremy Menez coming in for Florent Malouda and Debuchy.
"We had very few chances. We could have taken more risks but when you play against Spain, you run a lot and you lose your lucidity," said centre back Laurent Koscielny.
"But we gave everything, everybody fought on the pitch."
But being 1-0 down against a team who dominate possession makes it almost impossible to win, especially when you do not have a killer instinct.
"Scoring two goals when you don't have the ball much is really tough," said Blanc.
"On two or three occasions we had chances but we were a bit clumsy."
France leave the tournament with one win, a draw and two defeats. Although they made it to the knockout stages of a major tournament for the first time since the 2006 World Cup, they were never looked like beating Spain, rated as Euro 2012 favourites by Blanc.
"All the big nations will be in the semi-finals and unfortunately we will not be there," said Blanc.
"Germany and Spain are the top favourites."
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