The 28-year-old German, who wasn't originally down to ride the race, attacked the bunch on the Valkenberg and was joined by a select group of three riders.
Despite several climbs before the finish the German hung on, responding to attacks from his breakaway companions Lieuwe Westra (Vacansoleil-DCM Pro Cycling), Dmitriy Muravyev (Team RadioShack) and Vladimir Gusev (Katusha Team).
"I felt really good. It's something special for me today," the German said at the finish.
"At the end it was pretty tough but when Westra came from the back nobody wanted to ride anymore and they were attacking each other. I was just looking at him because he was the strongest today."
Greipel's aggression stemmed from his disappointment at finishing fourth in Gent-Wevelgem, with his team boss, Marc Sergeant, telling Cyclingnews that the rider had a "point to prove after finishing Sunday's race with mixed emotion."
"It's always nice to try something different for me," Greipel said. "For me it was just unexpected today. My teammate Jens Debusschere was in the breakaway today and when I came across I asked him to keep the speed up and he did a great job. It's his first year as a professional so it's also a victory for him today and the team."
Get The Leadout Newsletter
The latest race content, interviews, features, reviews and expert buying guides, direct to your inbox!
At his winner's press conference Greipel confirmed that Gent-Wevelgem had been a bitter-sweet day for him - pleased to have survived the punishing set of climbs he was one of the strong favourites to take the win but despite several teammates to help him in the finale he found himself caught too far back in the last few hundred metres.
"Yeah, I was really disappointed. You don't get so many opportunities to win a race like Gent-Wevelgem but today was another day and another race and we always tried our best as a team," he said.
As Greipel made his way back to the team bus, Sergeant looked on. "I was very impressed. It wasn't an easy stage for a sprint and he fought for every inch and every second. The four guys didn't work well together either, so it's a very good win. I'm really impressed," Sergeant said.
"Everyone knows he's more than a sprinter and this will give him a lot of confidence. He was with three good time trialists and they tried to get rid of him but he was too strong."
With two more road stages to come and a 14.7-kilometre time trial to conclude the race Greipel will have to ride as well if not better to wrap up the overall on Thursday. Sergeant confirmed that the team would look to defend the jersey in tomorrow's 219km stage from Oudenaarde to Koksijde.
"Everyone can still win this race because if you're a good time trialist you have a great chance. I hope we can win the overall and we'll look to defend the lead tomorrow, that's for sure."
Daniel Benson was the Editor in Chief at Cyclingnews.com between 2008 and 2022. Based in the UK, he joined the Cyclingnews team in 2008 as the site's first UK-based Managing Editor. In that time, he reported on over a dozen editions of the Tour de France, several World Championships, the Tour Down Under, Spring Classics, and the London 2012 Olympic Games. With the help of the excellent editorial team, he ran the coverage on Cyclingnews and has interviewed leading figures in the sport including UCI Presidents and Tour de France winners.
