The American No.8 seed will next meet former world No.3 Stefanos Tsitsipas, of Greece, a 2-6 6-1 7-6 (7-3) 6-1 winner over 18th-seeded Czech Jiri Lehecka.
With 23-year-old Shelton reaching the fourth round for the second time — the first coming in his breakout 2023 semi-final run — he is among a handful of local contenders looking to end a 23-year American wait for a men's grand slam singles champion after Andy Roddick's Flushing Meadows triumph.
Earlier on Friday (Saturday AEST), defending champion Carlos Alcaraz underlined his status as the man to beat with a ruthless 6-3 6-4 6-1 victory over Wu Yibing, as he reached the fourth round and continued his bid for a third title in New York.
The victory extended Alcaraz's match-winning streak at grand slams to 17 following his triumph at Flushing Meadows last year and his Australian Open win in February, the latter helping him to become the youngest man to complete the career Grand Slam.
The Spaniard arrived having missed nearly five months of action with a wrist injury and has looked increasingly assured with each passing round.
"After four months without competing ... when you play an official match with the nerves and everything, the day after or right after, your body can feel really tight," Alcaraz said.
"It didn't happen to me and I'm feeling better and better after every match."
World No.113 Wu was bidding to become the first Chinese man to make the last 16 of a slam in the professional era, but the seven-time major champion proved too strong and set up a meeting with American 20th seed Tommy Paul.
Daniil Medvedev has continued his strong form, beating Arthur Rinderknech 6-4 6-4 6-4.
The seventh-seeded Russian arrived in the Big Apple with plenty of room to move up the rankings, defending only 10 points after a chaotic first-round exit a year ago.
He also has history on his side, having won the US Open in 2021.
The only real scare came early, when he dropped serve for the first time in the tournament and Rinderknech, the No.29, moved 4-2 ahead.
The 30-year-old recovered quickly, winning four straight games to turn around the set and take the lead.
From there, Medvedev tightened his grip.
He did not face a single break point in the second set, serving with authority, while converting his only break opportunity to move two sets ahead.
He carried that momentum into the third, breaking Frenchman Rinderknech in the opening game to take a decisive lead and close out his 35th win of the year.
The victory avenged Medvedev's most recent meeting with Rinderknech, who beat him at the Shanghai Masters, while the Russian had won their previous encounter, also at the US Open, in straight sets in 2022.
Medvedev will face Frances Tiafoe, a comfortable winner over Rinderknech's cousin, Monaco's Valentin Vacherot, while there were also straight-sets victories for American Alex Michelsen and Argentine Tomas Martin Etcheverry.
18°C