Gilbert crashed on the descent of the infamous Col de Portet d'Aspet on stage 16 of the Tour, hitting a stone wall and plunging down the bank the other side.
Although he remounted and finished the stage, Gilbert's knee had swollen considerably, and hospital examinations revealed the fracture, meaning that his Tour was over.
The GP d'Isbergues – held halfway between Calais and Lille in northern France – was the 36-year-old Belgian's first race back having recovered from the injury.
Gilbert out-sprinted breakaway companion Christophe Laporte (Cofidis) for the victory, with Gilbert's Quick-Step teammate Florian Sénéchel taking the third spot on the podium.
"I've worked so hard to get back here today," Gilbert said on his team's website. "Honestly, there have been some difficult moments when I've been at home fighting to make this comeback. I've had a great team around me at home, but you still have to do the work yourself, to put in the energy and focus.
"After my crash, some of the most positive opinions I heard were that I should be happy if I was back on the bike within four months. Now I'm already back after two months, and I took my first victory of the season. My goal was to get a win in this last part of the season. I know it was a bit crazy, and 99 per cent of the riders would probably just be happy to come back, but I really believed I could do it."
Extremely heavy rain meant that the race organisers took the decision to shorten the course from 200km to 175km. Even so, Gilbert further demonstrated the strength of his return by attacking almost from the gun, and formed part of an 18-rider breakaway, which steadily decreased in size as the race wore on.
"The weather was really tough, especially in the final, when the temperatures dropped, but I actually felt good and was really confident," said Gilbert.
"When attacking with Laporte, we took advantage of the slippery roads from the rain and some tricky corners by going to the limit a few times, and in the last kilometres, seeing that Florian was coming from behind, I could save a bit of energy. In the final, I just felt I couldn't lose."
In the inaugural women's race, Australia's Lauren Kitchen won the race solo, 22 seconds ahead of her FDJ-Nouvelle Aquitaine-Futuroscope teammate Roxanne Fournier and Doltcini-Van Eyck Sport's Pascale Jeuland-Tranchant.