The world number one needed three tie-breaks to triumph 7-6 (7-3) 7-6 (7-4) 2-6 7-6 (7-4) in a closely contested encounter that ended just 27 minutes before the All England Club’s 23:00 BST curfew.
A Wimbledon finalist in 2021, Berrettini had been Italy’s leading man in tennis.
But there has been a changing of the guard, with 22-year-old Sinner’s success in recent years propelling him ahead of his Davis Cup team-mate.
“We are very good friends, we play Davis Cup together, sometimes we practise together,” Sinner said.
“It is very tough we had to face in the second round of such an important tournament.”
Berrettini, 28, was the world number nine when he became Italy’s first men’s singles finalist at Wimbledon three years ago.
Since then he has slipped down the rankings to 59th, with injury problems causing him to miss this year’s Australian Open and Roland Garros.
However, against Australian Open champion Sinner he showed his big serve has stayed put – hitting 28 aces to his opponent’s 10.
It was the younger Italian who took control of the opening two tie-breaks before Berrettini, roared on by the crowd, stormed through the third set.
But Sinner recovered from his brief blip, going toe to toe throughout the fourth before taking charge of another tie-break to close out the victory after three hours and 42 minutes.
“Today was a very high level match. I think we both played really well,” Sinner added, before telling the crowd: “It’s quite late so thanks for staying.”
Sinner will play Serbia’s Miomir Kecmanovic, who defeated Dutch 27th seed Tallon Griekspoor.
