After claiming a record fifth triumph in E3 Harelbeke on Friday, the Omega Pharma-Quick Step rider edged out Peter Sagan by a bike's length in a gallop to the line at the end of the 235km race.
The 31-year-old joined Robert Van Eenaeme, Rik Van Looy, Eddy Merckx and Mario Cipollini as the only three-time winners of the sprinters' classic.
A nine-man escape group formed shortly after the start at the market square of Deinze with Vladimir Isaychev, Koen Barbe, Stijn Neirynck, Kevin Van Melsen, Anders Lund, Jon Izaguirre, Yuri Krivtsov, Julien Fouchard and Thomas Bertolini building up a lead of over nine minutes during the flat opening half of the race.
The first of the 11 climbs came with 98km to go and their advantage began to whittle down in the 74th edition of the race with Lund (Saxo Bank) and Izaguirre (Euskaltel-Euskadi) going clear on the second ascent of the cobbled Kemmelberg with 37km remaining.
The chase group was strung out on that ascent, the penultimate of the 11 'hellingen', and Greg Van Avermaet injected a burst of pace on the final climb, the Monteberg, which followed soon after.
The BMC rider was joined by Fabian Cancellara and Slovak Sagan as an elite group formed but with a relatively flat 32km to the finish there was ample chance for regrouping and a lead bunch of 30 riders was established.
The group included many of the race favourites including Oscar Freire, Edvald Boasson Hagen and Matt Goss but the Norwegian's Team Sky team-mate Mark Cavendish was left marooned in a chase group 25 seconds behind.
With a lack of team support, the world champion saw the gap between the two groups increase and as his bid for victory was foiled, the lead group caught Lund and Izaguirre with 15km remaining.
A bunch sprint looked inevitable from that point and it was Boonen who became the first man to win the race in back-to-back years since Cipollini in 1993.
Liquigas rider Sagan was close behind with Matti Breschel, Freire and Boasson-Hagen completing the top five.
"The team once again was super strong," Boonen said. "(Gert) Steegmans in particular was a really key rider. Steegmans did something really unbelievable today. He kept the speed so fast so I could do my sprint.
"The entire team is showing its power. Other teams are as strong as ours, but we have to say this moment we are not so bad either. I am not a guy who screams at my team=mates, but with our team I don't have to say the same thing 10 times. Everybody knows what they have to do.
"I'm really happy to win Gent-Wevelgem. These races in Flanders, and Paris-Roubaix — I live for races like these. I like these and these are where I have to try and really perform even if every race I always do my best."
Meanwhile, Britain's Lizzie Armitstead won the inaugural women's event.