With five Americans playing in eight matches on the two steamy show courts, the home fans had plenty to cheer as the US men continued their push to end a 20-year US Open title drought.
An all-American clash kicked off the action on Arthur Ashe with 14th seed Paul taking on Shelton in a rematch of their Australian Open quarter-final.
Down two sets and 4-1 in third and staring at the exit, Paul fought back to prevent a rout but Shelton would not be denied, avenging his four set loss in Australia.
Paul was out smartly to a 3-0 lead but it was all down hill from there as the big-hitting Shelton blasted away, hammering down two 149 mph serves, the fastest seen at Flushing Meadows this fortnight.
Playing with swagger and energy, Shelton swept through six of the next seven games to snatch the first set and then dialled up the pressure with two late breaks in the second to go in front 2-0.
Shelton would put his opponent in a hole at 4-1 in the third but Paul continued to battle, loudly urged on by young superfan Eddy from Brooklyn, who has been in his corner all week including his comeback from a two-set deficit in the second round.
Paul would use two late breaks to win the third but there would be no way back against Shelton who held steady, breaking his compatriot to take the fourth set 6-4 and seal the win.
Check out the game summary with Flashscore.
It has been two decades since Andy Roddick became the last American man to win the US Open, and 2017 since Sloane Stephens hoisted the women's trophy, but as the season's final Grand Slam enters its second week there is a belief both finals next weekend could feature a home-grown contender.
For the first time since 2005 there will be three American men in the last eight, with Taylor Fritz, Frances Tiafoe and Shelton all posting last 16 wins.
And there is certain to be at least one U.S. man through to the semi-finals after Tiafoe swatted aside Australian wildcard Rinky Hijikata 6-4, 6-1, 6-4, and Shelton beat compatriot Tommy Paul 6-4 6-3 4-6 6-4 to set up a last eight all-American clash.
"Ben has wanted to play me at the Open for a long time," said Tiafoe, who electrified the tournament with his run to the semi-finals last year. "So he's going to be super excited. He's going to come out with a lot of energy.
"It's going to be a great atmosphere.
"Two people of colour playing in the quarter-finals, huge match on Arthur Ashe.
"It's a pretty monumental moment."
Fritz, who has not yet dropped a set, advanced with a tidy 7-6(2), 6-4, 6-4, win over Swiss qualifier Dominic Stricker.
His reward? A last-eight meeting with Djokovic.
Gauff was the first US woman into the last eight, ending Caroline Wozniacki's return to Flushing Meadows 6-3 3-6 6-1, and was probably preparing for a showdown with Swiatek until Ostapenko rewrote the script.
Top-ranked US woman Jessica Pegula, 2017 finalist Madison Keys and Peyton Stearns will all have their opportunity to join Gauff on Monday when they play their fourth-round matches.
"With Ben and Frances winning guarantees a person in the semi," said Gauff. "With Jess (Pegula) and Maddie (Keys) playing, it guarantees a person in the quarters.
"It's just really exciting tennis for America."
