The 20-year-old Michelsen followed up his shock first-round removal of world No.11 and 2023 Open runner-up Stefanos Tsistipas with a stunning straight-sets defeat of 19th seed Karen Khachanov on Saturday.
In claiming the two big scalps, Michelsen is the youngest American since dual winner Sampras and four-time AO champion Andre Agassi at the 1990 US Open to record multiple top-20 wins at a grand slam.
"I played unbelievable in that match. I don't even really know what's going on," Michelsen said after seeing off Khachanov 6-3 7-6 (7-5) 6-2 in two hours and 14 minutes.
"I was hitting my forehand unbelievable. I've never hit my forehand that well, so super happy to keep it going in the next round and, yeah, not a lot of words right now."
20-y.o. Alex Michelsen, who's beaten #12 Tsitsipas and #19 Khachanov at this — Christian's Court (@christianscourt) #AusOpen, is the youngest American man to claim multiple top 20 wins at a major since Sampras and Agassi at the 1990 US Open. Does Michelsen have what it takes to win a slam � in his career? pic.twitter.com/A6tGa2IlHdJanuary 18, 2025
Khachanov was a semi-finalist at Melbourne Park two years and shaped as a road block between Alex de Minaur and a place in the quarter-finals for the first time for the eighth-seeded home hope.
Instead Michelsen will be standing in de Minaur's way after the Australian eighth seed survived a third-round scare to take care of Argentina's world No.31 Francisco Cerundolo 5-7 7-6 (7-3) 6-3 6-3.
Fellow American youngster Learner Tien continued his fairytale Open debut, grinding down weary Frenchman Corentin Moutet 7-6 (12-10) 6-3 6-3 in two hours and 49 minutes.
American teenage qualifier Learner Tien has continued his incredible Open run. (Lukas Coch/AAP PHOTOS)
The 19-year-old qualifier, who slayed Russian world No.5 Daniil Medvedev in the previous round, is the youngest man to make the last 16 at Melbourne Park since 22-time major winner Rafael Nadal lost to Lleyton Hewitt in 2005.
"I don't think I can compare myself to Rafa but that's cool," said Tien, who will face Lorenzo Sonego for a quarter-final spot after the Italian took down Hungarian Fabian Marozsan 6-7 (3-7) 7-6 (8-6) 6-1 6-2
In the searing heat on Kia Arena, Moutet fell awkwardly after a serve early in the third set and began writhing in pain on the ground.
"I didn't really know what happened," Tien said.
"But he told me he was going to keep trying just for me."
While Michelsen and Tien marched on, fourth-seeded countryman Taylor Fritz was eliminated by French veteran Gael Monfils, who continued to wind back the clock with a 3-6 7-5 7-6 (7-1) 6-4 boilover.
The 38-year-old extended his hot run of form, taking his record to 9-1 for the season with an eighth straight victory after winning the Auckland title earlier this month.
A two-time Open quarter-finalist in 2016 and 2022, Monfils can match his previous best result if he beats either Ben Shelton or Lorenzo Musetti in the fourth round.