Defending champion Alcaraz, who has only dropped one set on his journey into the last eight, produced a dominant display to overwhelm world No.61 Arnaldi, winning 6-3, 6-3, 6-4 in 1hr 57min.
The 20-year-old Alcaraz is bidding to become the first man since Roger Federer in 2008 to successfully defend the US Open after winning the title for the first time last year.
The identity of the Spaniard's quarter-final opponent will be confirmed later Monday, with Alcaraz due to face either Germany's Alexander Zverev or Italy's sixth seed Jannik Sinner in the last eight on Wednesday.
A match with Sinner would be a repeat of last year's quarter-final classic between the two men, which set a record as the latest ever finish for a US Open game after wrapping up at 2.50am.
"I think the intensity from the beginning until the last ball, I played a really solid match, less mistakes," Alcaraz said after Monday's brisk victory.
"I'm really happy with the performance in general."
In other men's matches on Monday, Britain's Jack Draper takes on eighth-seeded Russian Andrey Rublev while third seed Daniil Medvedev, the 2021 champion, faces Australian 13th seed Alex de Minaur.
Pegula sunk by friendly fire
In the women's draw meanwhile, Pegula joined world number one Iga Swiatek - upset in the fourth round on Sunday - in heading for the tournament exit, losing in straight sets to compatriot and close friend Madison Keys.
Pegula had gone into the US Open dreaming of a first ever Grand Slam, buoyed by victory in last month's WTA 1000 Canadian Open in Montreal.
But the 29-year-old's campaign came to an abrupt halt in front of a packed Arthur Ashe Stadium as 2017 US Open finalist Keys recorded a dominant 6-1, 6-3 win in just 61 minutes.
Pegula was left with no answer as Keys unleashed a stream of 21 winners to her six.
Keys also punished her friend's shaky serve, breaking her five times on her way to wrapping up a comfortable victory.
"It's always tough having to play a friend but we've been doing it our whole lives at this point," Keys, 28, said.
"When we get on the court it's all business and when we get off the court we go back to being friends."
The 17th-seeded Keys will now face Wimbledon champion Marketa Vondrousova of the Czech Republic in the quarter-finals on Wednesday.
Ninth seed Vondrousova booked her place in the last eight with a battling win over unseeded American Peyton Stearns, coming from a set down to win 6-7 (3/7), 6-3, 6-2.
Vondrousova made history in July after becoming the first unseeded woman to win Wimbledon, her first Grand Slam title.
The 24-year-old has never been past the fourth round at the US Open, and admitted after her win on Monday she had surprised herself by advancing to the last eight.
"She was playing great from the beginning, and I just tried to stay in the game," Vondrousova said of Stearns.
"I'm very happy. I actually didn't expect it after Wimby - it was a lot of pressure. We'll see what happens next."
Two other women's quarter-finalists will be decided later Monday, with second seed Aryna Sabalenka - destined to be the new women's world number one after Swiatek's demise on Sunday - facing Russia's Daria Kasatkina.
Tunisia's fifth-seeded Ons Jabeur faces China's Zheng Qinwen in the other women's fourth round clash.
