This year's US Open has seen 24-time Slam winner and four-time New York champion Novak Djokovic suffer his earliest exit in 18 years.
Carlos Alcaraz, the 2022 champion and winner this year at the French Open and Wimbledon, was also a first-week casualty.
Five-time US Open champion Roger Federer is long retired while Rafael Nadal, a four-time winner, is 38 and absent from this edition, heading into the twilight of his career.
"It was only a matter of time, the game is open. It's not like it once was where you make quarter-finals, you play Rafa, and you're looking at flights," said Tiafoe.
"Now it's just totally different and no one's unbeatable, especially later in the season where guys are maybe a little bit cooked.
"Maybe just not as fresh and they're vulnerable. It's pretty exciting."
Tiafoe, the 20th seed, progressed to the semi-finals on Tuesday after ninth-ranked Grigor Dimitrov suffered an injury in the third set of their quarter-final and quit in the fourth with the score at 6-3, 6-7 (5/7), 6-3, 4-1.
Tiafoe also reached the last four in 2022 while Fritz booked a place in his first Grand Slam semi-final by defeating 2020 runner-up and fourth-ranked Alexander Zverev 7-6 (7/2), 3-6, 6-4, 7-6 (7/3).
Andy Roddick was the last American man to win a Grand Slam title when he claimed the 2003 US Open.
He was also the last home player to make a final in New York when he was defeated by Federer in the 2006 championship match.
Friday's semi-final will be the first all-American men's singles last-four clash since Andre Agassi defeated Robby Ginepri at the 2005 US Open.
