Alaphilippe's brutal acceleration on the last climb of the 258.2km race left his rivals in his wake and the Frenchman eased to the line with Fleming Wout van Aert having to settle for silver. Swiss Marc Hirschi took bronze.
Three years after coming close in Bergen, Norway, when he was reined in with one kilometre to go, Alaphilippe benefited from top work by the French team, with Guillaume Martin covering their opponents' attacks on the penultimate ascent.
As Alaphilippe turned on the power 12km from the finish on the last of nine 28.8-km laps, only a handful of top riders - Jakob Fuglsang, Hirschi, Van Aert, Primoz Roglic and Michal Kwiatkowski - were left to chase.
They were unable to catch him before the final kilometres on Imola's former Formula One track, where they started to prepare for the sprint for second place, leaving Alaphilippe to celebrate the title.
"It's hard for me to say something. I want to say thank you to all my team mates who believed in me today," a tearful Alaphilippe, the first Frenhcman to win the title since Laurent Brochard 23 years ago, said.
"We did a great job. It was the dream of my career. I came so close already but never made it to the podium. I came with a lot of ambition, it's just a dream come true." (Writing by Julien Pretot; Editing by Ed Osmond).