Last year's Paris-Roubaix winner Niki Terpstra took second at the end of the 240km race in dreadful conditions with blustery winds and driving rain as Friday's E3 Harelbeke winner Geraint Thomas came third.
With winds of up to 90kph (56mph) the race became an interminable slog and a battle of wills but it was Paolini's opportunistic attack just under 6km from home to distance his five breakaway companions that proved decisive.
"It was an incredible race, one for the courageous," said Paolini, who crashed twice and had to change his bike during the day.
"Halfway through I was asking myself if it was reasonable to continue. But I resisted (the temptation to quit) and I've earned the best win of my career."
After winning in 6hr 20min 55sec, Paolini added: "This victory is one for heart, courage but also intelligence.
"I possibly wasn't the strongest at the finish. Niki Terpstra and Geraint Thomas still had strong legs, but they were worried about each other and I took my chance."
The 38-year-old Katusha rider had fought gamely to join the other five following the final climb of the race around 30km from the finish of the second of four cobbled classics.
Dutchman Terpstra, Briton Thomas and Belgians Stijn Vandenbergh, Sep Vanmarcke and Jens Debusschere were chasing down a sole leader at that time, Jurgen Roelandts.
Paolini managed to bridge the gap but compatriot Daniel Oss failed to do so as a six-man chase group formed.
Debusschere sat at the back as Belgian Roelandts rides for the same Lotto Soudal team.
However, he was caught 17km from the end, after which Terpstra and Paolini struck out for home.