The British star prevailed in a bunch sprint at the end of a 204.2km stage from Oudenaarde to Koksijde.
The Omega Pharma-QuickStep train hit the front over five kilometres from home but a strong headwind saw their numbers dwindle, prompting the Manx missile go from a long way out.
The 27-year-old former world champion had the raw strength to hold off the fast finishing Elia Viviani (Cannondale) and Francesco Chicchi (Vini Fantini) for his seventh stage win of the year.
Mattia Pozzo (Vini Fantini-Selle Italia), Gregor Gazvoda (Champion System), Tim Mertens (Topsport Vlaanderen-Baloise), Kevin Claeys (Crelan-Euphony) and Niko Eeckhout (An Post-Chainreaction) were involved in the break of the day.
They went away early and had built a maximum lead of 8:25 after 86km.
But a split in the peloton behind caused the pace to soar and with 60km remaining, the escapees had been caught and the race was all back together.
Alessandro Bazzana (UnitedHealthcare), Dmitriy Gruzdev (Astana) and Koen Barbe (Crelan-Euphony) then launched a counter-attack and gained a lead of over two minutes but the stage concluded with a short circuit and the trio were reeled back inside the final 10 kilometres to set up the inevitable gallop to the line.
And Arnaud Demare (FDJ) took fourth place in the sprint to claim the overall race lead from Peter Sagan. The insatiable Slovak finally paying the price of his recent exertions, which included victory in Sunday's Gent-Wevelgem and Tuesday's opening stage, by being dropped in the final stages.
The four-stage Europe Tour event concludes on Thursday with a 112.6km road stage in the morning before the GC will be decided by an individual time trial of 14.75km in the afternoon.