It was a breathtaking display from the 2010 World Cup winners, with victory all but sealed by halftime as goals from David Silva and Jordi Alba gave them a 2-0 lead.
Substitutes Fernando Torres and Juan Mata rounded off the emphatic win with two late strikes.
Victory in the final also represents a triumph for 61-year-old coach Vicente Del Bosque, the first man to lead teams to the World Cup, European Championships and European Champions League crowns, the latter with Real Madrid in 2000 and 2002.
But for Italy and their coach Cesar Prandelli it was a bitter end to a tournament which they had earlier graced with their imaginative performances.
La Roja shone brightly from the start and with a cutting edge, despite again starting the match without a recognized striker.
Barcelona's Xavi Hernandez brushed the crossbar with a fierce shot in the 10th minute after dazzling interplay but it did not take long for the pressure to pay off.
Xavi's club teammate Andres Iniesta threaded a perfect pass through for Cesc Fabregas to cross for David Silva to head home on 14 minutes.
Italy, who caused such a shock with a 2-1 win over Germany in the semifinals, responded with a pair of Antonio Cassano efforts, but with Mario Balotelli unable to make much impression they always looked second best.
Spain went further ahead just before halftime and the goal was typical off their all round teamwork.
Defender Jordi Alba exchanged passes with Xavi and burst through the center of the Italian defense before easily beating Gianluigi Buffon.
After the break, Italy responded with a pair of chances for Antonio di Natali, the first a header, the second with a clearer sight of goal only to be denied twice in quick succession by Spain captain Iker Casillas.
Italian hopes of a comeback took a further dent when their final substitute, Thiago Motta, lasted only five minutes before being stretchered off.
Against a tiring team with only 10 men, Spain eventually took full advantage after the introduction of Chelsea's Torres.
Xavi found him with another superb pass and he slotted home the third on 84 minutes, becoming the first man to score in two successive European Championship finals. .
Torres then set up his club teammate Mata to score with virtually his first touch of the ball.