Shelton, the son of former professional Bryan Shelton, is blessed with a big serve and booming forehand but he showed he had plenty of resolve too, beating compatriot Frances Tiafoe (25) 6-2, 3-6, 7-6(7), 6-2 at a muggy Arthur Ashe Stadium.
He will need all of his weapons on Friday if he is to stand a chance in his first meeting with Djokovic.
"I think that it's an advantage with my game style, playing someone who's never played me before," Shelton told reporters.
"I think that I can bring some things to the table that maybe you don't see in your normal match that you play on the ATP Tour.
"So I'm definitely going to try to bring some things to the table that are different and hopefully disruptive on Friday."
But playing second seed Djokovic is never a normal match.
The Serb, who is looking to match Margaret Court's all-time record of 24 major singles titles with a fourth Flushing Meadows crown, will be competing in a record 47th Grand Slam semi-final.
Shelton will be playing in his first.
"I think whenever you play somebody for the first time and someone who has been in this situation so many times and come out victorious so many times, that's in the back of your head," Shelton said.
"You just know how rock solid the guy is and how mentally tough, how physically tough. So that's definitely something that I have to game-plan for."
