World number 91 Ebden had surprised everyone by forcing his way through to the last 16 in California, but the American had too much class and power for him, taking it 6-4 7-5 in clinical fashion.
Ebden began the match confidently and won his first two service games with ease, but failed to make any ground against the gigantic 11th seed on return.
The 24-year-old came unstuck at 2-2, handing the American his only break point opportunity of the set which Isner duly converted, ruthlessly so.
Ebden was unable to produce a return break to level the set, and won just four points against Isner's serve in the first set.
The second was more of the same as both players held serve comfortably and rarely looked threatened.
Ebden created the first break point opportunities of the set when leading 4-3, but Isner produced two huge second serves on both occasions to see off the danger.
At 5-5 it was Ebden's turn to look vulnerable, and unlike Isner, he was not able to serve his way out of trouble when he needed to as the American claimed the decisive break before serving out the match.
Isner will next take on 13th seed
Simon appeared to have the match wrapped up in straight sets as he moved into a 5-2 lead in the second but a remarkable fightback from Harrison saw him claim five consecutive games to take it to a decider.
That was all Harrison had though, and Simon eased through the final set to clinch victory and a place in the last eight.