Rafael Nadal's loss to Frances Tiafoe opened up a host of possibilities including a first-time world number one and maiden grand slam winner as the top three's domination of men's singles continues to weaken.
World number three Nadal bowed out in the fourth round to 22nd seed Tiafoe 6-4 4-6 6-4 6-3 on Monday, while third seed Alcaraz triumphed over Marin Cilic 6-4 3-6 6-4 4-6 6-3 in a match that went to almost 2:30am local time.
Cilic was the last remaining male player with a grand slam title to his name, meaning this year's US Open will bring a new major champion.
There may also be a first-time world number one too, with Alcaraz guaranteed to claim the top rank if he wins the US Open title.
Fifth seed Casper Ruud will rise to world number one if he lifts the US Open crown at Flushing Meadows on September 11 too.
If both fall short of the final, Nadal will reclaim the top ranking from 2021 US Open champion Daniil Medvedev, who lost in the fourth round to Nick Kyrgios.
Alcaraz could also scale the rankings summit should he reach the final, assuming Ruud misses out.