Zverev, who had been taken to five sets in his opening two matches of the tournament, raced past 21st seed Darderi 6-2, 6-2, 7-6 (3) in 2hr 30mins on the Arthur Ashe Stadium court.
The 29-year-old French Open champion was in complete control throughout, punishing Darderi's woeful service game to grab an early double break in the first set for a 3-0 lead.
Darderi, who has failed to go further than the fourth round at any Grand Slam in his career, never looked like forcing his way back into the set thereafter.
Zverev mopped up the first set easily and was soon back on the attack in the second, once again securing a quick double-break for a 3-0 lead before holding with ease to go two sets up.
Darderi did manage to rally in the third set, suddenly finding his range with some blistering forehands and holding off four break points in the 11th game to help set up a tie-break.
But Zverev's superior service game meant there was only going to be one winner in the tie-break, a thunderous serve giving him a 5-2 lead before a scorching forehand into the corner took him to match point.
Zverev then wrapped up victory with his 13th ace of the game and will now face Dutch veteran Botic van de Zandschulp in the quarter-finals.
US Open 2026
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