His retirement from the match also calls into question his US Open Challenge, with the final grand slam event of the year just a month away.
John Isner (USA) reacts during his match.
Ebden is 1-3 against Isner but won their past meeting in January at the Australian Open.
52 minutes into his quarter-final match against Britain's Cameron Norrie, the second-seeded Australian was down 5-7 0-3 when he retired hurt due to some issue with his hip.
Isner, who is ranked No. 9 in the world, will seek his second title of the season and the 14th of his career.
"I benefited from my opponent not being 100 percent", Isner said. "That's how our sport goes sometimes, and I was very fortunate today". "I was struggling a little bit", Isner, a four-times champion in Atlanta, said. "There are no secrets there".
Isner dropped just two first-serve points in the match and sent down 21 aces. "I really feel for the guy", he was quoted as saying. He had the home crowd on his side.
"Now, I'm playing in my backyard and he beat me in his backyard. But we'll see what happens". He will face the victor of Friday night's match between Brit Cameron Norrie and second-seeded Australian Nick Kyrgios in the other semifinal.
But Isner acknowledged he had been fortunate to prevail over Harrison, the eighth seed, who took the first set and was clearly the better player early in the second.
Of the four winners, Mayer is the highest ranked at No. 36. Djere barely got by Croatian Viktor Galovic 6-7 (5), 6-3, 7-6 (5).
Bautista Agut, ranked 17th in the world, topped Serbian Laslo Djere 6-7 (5), 6-4, 6-4 in the other semifinal. Zopp topped Argentina's Facundo Bagnis 3-6, 6-4, 6-3 in a battle of qualifiers.