The Omega Pharma-Quickstep rider edged out three-time world champion Oscar Freire in a sprint finish at the end of the 203km race that began and ended in Harelbeke.
Surprisingly around 40 riders were still together under the Flamme Rouge after a break failed to stick in the mini Tour of Flanders which included 13 climbs.
A nine-man escape group formed during the flat opening half of the race featuring the Farnese Vini trio of Luca Ascani, Oscar Gatto and Kevin Hulsmans plus Gert Dockx, Gregor Gazvoda, Michael Morkov, Nico Sijmens, Sebastien Delfosse and Damien Gaudin.
They built up a lead of over five minutes, aided by the peloton being held at a level crossing, but the lead was soon whittled down as they tackled the baker's dozen of hellingen.
Boonen initiated a move on the seventh of those ascents, the Taaienberg, with 55km left and an elite group formed minus one of the race favourites Philippe Gilbert (BMC) who abandoned shortly afterwards.
But they were soon caught by the peloton as the short, sharp climbs took their toll on the escape group with Italian Gatto the lone survivor of the original escape and holding a 45-second lead ahead of the pivotal Oude Kwaremont with 36km remaining.
Two-time defending champion Fabian Cancellara powered up the Oude Kwaremont with Boonen in his wheel before the Swiss suffered a front puncture and lost ground.
And his hopes of a hat-trick of victories looked over when he was hit by Rabobank's Carlos Barredo whilst receiving mechanical assistance.
Gatto was caught by Sylvain Chavanel and Dmitriy Muravyev after the penultimate climb of the Knokteberg but the Boonen-led chase group failed to co-ordinate their efforts and were caught by the peloton, including Spartacus, on the run back to Harelbeke.
Chavanel and Muravyev were reeled in with 7km remaining and an unusually large bunch came to the finish with Boonen pipping the Katusha rider from Spain by little more than a width of a wheel rim.
Second-placed Freire said: “I’m quite disappointed. I felt in a really good shape and I could have easily won the final sprint because, in the end, I was faster than Boonen.
“Unfortunately, he knows this course by heart, and most of all the end; I think that's the reason why I only finished second. He made a really good sprint - he was perfect - and instead I made a mistake so I started my rush too late.”
Team Sky's Bernhard Eisel was third ahead of Leonardo Duque, Sep Vanmarcke and John Degenkolb with Cancellara paying the price for his earlier efforts.