The 18-year-old twice held his nerve in a tiebreak and also recovered from an annihilation in set four to record a 6-3, 4-6, 7-6, 0-6, 7-6 win.

Tsitsipas' exit represents the biggest upset of Grand Slam in New York City so far.

Alcaraz had three match points in the fifth-set tiebreak and thought he had won the encounter with a lob which left Tsitsipas stranded - but the ball bounced out by a fraction of an inch.

The Spaniard regained his composure and, having squandered two match points, won a third on the Tsitsipas serve with a viscous forehand winner before collapsing to the hard court in ecstasy. 

"I think without this crowd I hadn't the opportunity to win this match," Alcaraz said afterwards, grateful for the support.

Defeat caps a miserable few weeks in North America for Tsitsipas, who has faced stinging criticism from fellow players including British two-time Olympic champion Sir Andy Murray for the length of his toilet breaks, causing the crowd to root for his opposition.

Tsitsipas' stance on COVID-19 vaccinations - that he would not get one unless mandated to by the Association of Tennis Professionals - was also pilloried by a Greek Government spokesperson, who said the 23-year-old "has neither the knowledge nor the studies nor the research work that would allow him to form an opinion about it [the vaccine]."

Elsewhere at the Billie Jean King National Tennis Center, second seed Daniil Medvedev breezed into the fourth round.

The Russian beat Spain's Pablo Andújar 6-0, 6-4, 6-3 inside two hours.

Diego Schwartzman, the Argentine 11th seed, won through in straight sets, while Briton Dan Evans staged a superb comeback from two sets behind.

Despite conceding 18 aces, Evans overcame Australia's Alexei Popyrin 4-6, 3-6, 6-3, 6-4, 7-6.

Later in the evening, Russia's number five seed, Andrey Rublev, lost to home hero Frances Tiafoe in a five-set thriller.

After Rublev drew level in the fourth set, Tiafoe ran away with the fifth, winning 4-6, 6-3, 7-6, 4-6, 6-1.

Rublev will face Canada's Félix Auger-Aliassime, ranked 12th, who overcame 16th seed Roberto Bautista Agut of Spain in another gruelling five-set victory.

Auger-Aliassime had won the first two sets, only for Bautista Agut to work his way back into the match, before faltering in the fifth set.