In a rain-affected race, the 24-year-old Dutchman came home 16.5 seconds ahead of his Red Bull teammate as Charles Leclerc and Ferrari endured a disappointing day in front of passionate home support at the Autodromo Enzo e Dino Ferrari.
Leclerc, who started second on the grid, finished sixth after making a poor start and spinning in the closing laps while running third, allowing Lando Norris to take third for McLaren.
After Saudi Arabia, it was Verstappen's second win this season which has also included two retirements, and the 22nd win of his career.
He reeled off a 'grand slam' weekend with pole position, victory and fastest lap as well as victory in Saturday's sprint race.
He moved up to second in the title race behind Leclerc, reducing his deficit from 45 points to 27 to set up the prospect of an intense duel this year between them and their teams.
"It's always tough to achieve something like that, but already yesterday and the day before, we were on it," said Verstappen.
"And it was looking like a strong weekend. You never know with the weather how competitive you are going to be, but I think we did very well and this one-two is very deserved.
"The start was very important, but afterwards, judging the conditions and when to swap to the slick tyres – because in the lead you have to always dictate the pace."
Perez said he was delighted to bring smiles to the Red Bull team.
"It was really intense," he said. "The most important thing today was not to make mistakes because with these conditions it was so tricky. To get a one-two, out there, is a great result for the team.