Defending champion Alcaraz, who has only dropped one set on his journey into the last eight, produced a dominant display to overwhelm Italian world No.61 Matteo Arnaldi, winning 6-3, 6-3, 6-4 in 1hr 57min.
Alcaraz will face 12th seed Alexander Zverev in Wednesday's quarter-finals after the 2020 US Open finalist from Germany defeated Italian sixth seed Jannik Sinner in a five-set duel tinged with controversy.
Zverev, who is returning to his best form after a gruesome injury at the French Open last year that forced a six-month layoff, downed Sinner 6-4, 3-6, 6-2, 4-6, 6-3 on the Arthur Ashe Stadium.
The 4hr 41min battle, which wrapped at 1.39am local time, saw an ugly incident in the fourth set when Zverev complained of a "Hitler phrase" being shouted from the stands as he prepared to serve.
"He just said the most famous Hitler phrase there is in this world," Zverev told the umpire. "This is unbelievable."
A male fan was subsequently identified as the alleged culprit and ejected from the arena before Zverev went on to seal victory.
"I love when fans are loud, I love when fans are emotional but I think me being German, and not really proud of that history, it's not really a great thing to do," Zverev said of the incident afterwards.
"If I just don't react I think it's bad from my side."
In other men's matches on Monday, eighth-seeded Russian Andrey Rublev advanced with a 6-3, 3-6, 6-3, 6-4 defeat of Britain's Jack Draper.
Rublev will now face an all-Russian quarter-final against close friend Daniil Medvedev, the third-seeded 2021 US Open champion who punched his ticket to the last eight with a 2-6, 6-4, 6-1, 6-2 defeat of Australian 13th seed Alex de Minaur.
Rublev, who has known Medvedev since childhood, is godfather to his quarter-final opponent's daughter.
Pegula sunk by friendly fire
In the women's draw meanwhile, more seeds bit the dust a day after world number one and defending champion Iga Swiatek was sent packing in the fourth round.
American third seed Jessica Pegula was routed in straight sets by compatriot and friend Madison Keys, while Tunisia's fifth seed Jabeur -- beaten in last year's final -- was ousted 6-2, 6-4 by China's Zheng Qinwen.
Pegula'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.
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.
Jabeur meanwhile, who has been struggling with flu since arriving in New York, finally saw her luck run out after scrapping her way to three-set victories in her previous two games.
The Tunisian simply had no answer to 23rd seed Zheng's blend of power and precision, with the 20-year-old from Shiyan looking far sharper than her weary opponent.
"Right now I feel just super happy and excited to play in a big stadium. I had a really good performance today," said Zheng.
Zheng is China's first US Open quarter-finalist since Wang Qiang in 2019. Two-time major champion Li Na reached the semi-finals in New York in 2013 and Peng Shuai did the same a year later.
Zheng's quarter-final assignment is a daunting date with second seed Aryna Sabalenka, who celebrated her rise to the pinnacle of women's tennis by routing Russia's Daria Kasatkina 6-1, 6-3 to secure her last eight berth.
Swiatek's exit on Sunday guarantees that the 25-year-old Belarusian will become the new world number one when the latest global rankings are released next week.
"It means a lot to me," Sabalenka said of her No.1 ranking after defeating Kasatkina.
"I've been pushing myself all this year to reach this goal. It's unbelievable, it's something crazy, I still can't believe it."
(For more sports news and updates, follow Ahram Online Sports on Twitter at @AO_Sports and on Facebook at AhramOnlineSports.)