"When I came into the match I had nothing to lose as everyone was expecting him to win," said the unseeded Australian, who fired 46 aces on his way to a 6-3, 2-6, 6-7, 6-3, 6-4 win over Agassi.
"I hung in there and fought hard. This win is definitely up there. It was extremely important for me to win because I think he'd beaten me the last (six) times in a row.
"So to finally get him , and the way it happened, I'm just very pleased.
"Every match here I've played better and better and my confidence is going up."
Agassi had beaten Philippoussis in the 2000 quarter-finals here, but the Australian had done his homework well and felt it was now his time to snap the losing streak.
Philippoussis, the 1998 U.S. Open runner-up to compatriot Pat Rafter, has had to endure three knee operations since 1999 and is hoping that he will at last get past the last eight hurdle on his seventh visit to the championships.
OMNIOUS FORM
The big-serving Philippoussis especially wants to make up for his disappointment in 1999
He even had then five-times Wimbledon champion Pete Sampras reeling in the last eight by blasting his way to a one-set lead before a cartilage tear in his left knee forced him to retire in the second set.
With the unseeded German Alexander Popp blocking his path to the semi-finals, the world number 48 was optimistic about his chances to go further in the tournament.
"The great thing is I don't have any knee pain at all. There's no niggling pains, nothing that's sore. It feels great," said the 26-year-old.
"I'm pleased with the work today and hope I can go on," "I've got to try and take the pluses from that match and put it into my next match.
"I've been in the quarter-finals a few times so that will help with the experience."
"He's a dangerous player and has got a great serve and big weapons so I'm just going to watch out."