Unseeded Philippoussis unleashed an astonishing 46 aces, equalling the all-time Wimbledon record for a single match, to beat the second seed and world number one 6-3, 2-6, 6-7, 6-3, 6-4 in a fourth-round epic on court one.
"To finally get him, and the way it happened, I'm just very pleased," said the Australian, who had lost his previous six matches against Agassi.
Philippoussis's victory ruined an otherwise superb day for the Americans. Andy Roddick sealed his quarter-final place and the four leading American women, Serena and Venus Williams, Lindsay Davenport and Jennifer Capriati all swept through to the last eight after a rain-delayed start to the day.
British hopes of a first home men's winner since 1936 remained alive after Tim Henman defeated last year's runner-up, Argentine David Nalbandian 6-2, 6-7, 7-5, 6-3, to reach the quarter-finals for the seventh time in eight years.
Henman will now play either Spanish third seed Juan Carlos Ferrero or Frenchman Sebastian Grosjean. Grosjean led 6-2, 4-6, 7-6 when play was stopped due to bad light.
RUSSIAN WOE
Russia suffered as four of their five women lost, including shrieking 16-year-old wild card Maria Sharapova, but Belgian duo Justine Henin-Hardenne and Kim Clijsters moved through to the quarter-finals as expected.
Philippoussis, ranked 48, equalled Goran Ivanisevic's 1997 record of 46 aces in a single match at the All England Club to leave 33-year-old Agassi forlorn and exhausted after the best match so far of the men's draw.
The win ended a run of six straight defeats by Agassi and avenged his 2000 Wimbledon quarter-final defeat by the 1992 champion.
Agassi's defeat followed the shock first-round exit of defending champion Lleyton Hewitt in the first round. It means there is no previous winner in the men's quarter-finals for the first time since 1973.
Philippoussis next plays German Alexander Popp, a quarter-finalist at Wimbledon three years ago, who made the most of his 14-inch (35cm) height advantage over Belgium's Olivier Rochus to win 5-7, 6-3, 6-4, 6-2.
Roddick convincingly saw off 12th-seed Thai Paradorn Srichaphan 6-4, 3-6, 6-3, 6-2, although he was made to fight by the Thai.
The 20-year-old American, seeking his first grand slam title, faces an unseeded player in the last eight in Sweden's Jonas Bjorkman who beat Belarussian Max Mirnyi in four sets.
Roddick is still on course for a semi-final meeting with talented Swiss fourth seed Roger Federer, who beat Spain's Feliciano Lopez 7-6 6-4 6-4 despite play through back pain after injuring himself warming up.
CONFIDENT CLIJSTERS
Federer's quarter-final opponent, assuming he is fit, is Dutch eighth seed Sjeng Schalken, who ousted Australian Open runner-up Rainer Schuettler of Germany in three sets.
The six favourites for the women's crown -- the American quartet plus Henin and Clijsters -- again had an easy time of it.
Not one of them has dropped a set in the tournament so far.
Serena out-clubbed Russian Elena Dementieva 6-2, 6-2 on Centre Court and will next face Capriati, seeded eighth, after she demolished Anastasia Myskina 6-2, 6-3.
Capriati is the last player to have beaten Serena at Wimbledon. She won their epic 2001 quarter-final in three sets.
Fourth seed Venus, the 2000 and 2001 Wimbledon champion, avenged her French Open defeat by Russian Vera Zvonareva 6-1 6-3 to set up another all-American quarter-final against fifth seed Lindsay Davenport.
Davenport brushed past Japan's Shinobu Asagoe, winning 6-4, 6-1.
French Open champion Henin, barely hindered by her painful hand injury, outclassed Frenchwoman Mary Pierce 6-3, 6-3 to set up a quarter-final with Wimbledon debutante Svetlana Kuznetsova of Russia. Kuznetsova defeated Sharapova 6-1, 2-6, 7-5.
Confident Clijsters, the second seed, humbled her doubles partner Ai Sugiyama of Japan 6-3, 6-2.
It was Clijsters' 50th singles win of the year. Not since Martina Navratilova in 1982 has a woman player reached her half-century so early in the season.
Italy's Silvia Farina Elia awaits the hard-hitting Belgian in the last eight after her straight sets win over Paola Suarez of Argentina.
