But while 2002 champion Hewitt had a packed Center Court on its feet, it was business as usual in the women´s draw as five-time champion Venus Williams, French Open winner Svetlana Kuznetsova and world number one Dinara Safina eased into the last 32.
The 28-year-old Hewitt demolished giant Argentine del Potro, eight years his junior, 6-3, 7-5, 7-5 to reach the third round for the ninth time and now tackles either Philipp Petzschner or Mischa Zverev for a place in the last 16.
The Australian, whose ranking has slipped to 56 following hip surgery, collapsed to his knees in celebration at the end.
"I haven´t beaten a top five player for a long time," said Hewitt.
"I was really up for it today. When you have played a final on Center Court you should be able to handle the pressure but I knew that Juan Martin is a helluva player."
Third-seeded Venus Williams, the defending champion, took only an hour to see off Ukraine´s Kateryna Bondarenko 6-3, 6-2 while Russian fifth seed Kuznetsova spent just four minutes longer in disposing of France´s Pauline Parmentier 6-1, 6-3.
Williams goes on to face Spain´s Carla Suarez Navarro while Kuznetsova, a three-time quarter-finalist here, meets promising German Sabine Lisicki.
"Everything was working for me. I´m on a great run here and I just want to keep it going," said Williams, who played with heavy strapping on her left knee.
Safina, still looking for a first Grand Slam debut to back-up her number one status, saw off Paraguay´s Rossana De Los Rios 6-3, 7-5.
The Russian next plays Belgium´s Kirsten Flipkins who ended British interest in the women´s singles with a 7-5, 6-1 win over Elena Baltacha.
Australian 18th seed Samantha Stosur, a semi-finalist at the French Open, struggled past German qualifier Tatjana Malek 4-6, 7-6 (8/6), 6-4 and will face former world number one Ana Ivanovic.
In the men´s event, Czech 20th seed Tomas Berdych, Jurgen Melzer, the 26th seed from Austria, and Romanian 31st seed Victor Hanescu all made the last 32.
Later Thursday, world number three Andy Murray tackles stylish Latvian Ernests Gulbis for a place in the third round as he continues his campaign to end Britain´s 73-year wait for a men´s champion.
Two-time runner-up Andy Roddick reached the Wimbledon third round with a 6-4, 6-2, 3-6, 6-2 win over Russia´s Igor Kunitsyn. The American sixth seed faces Austria´s Jurgen Melzer for a place in the last 16.
Meanwhile, Ana Ivanovic restored the reputation of Wimbledon´s glamor girls with a 7-5, 6-1 victory over Italy´s Sara Errani in the second round on Thursday.
After Russian beauty Maria Sharapova crashed out of the tournament against Argentine Gisela Dulko on Wednesday, Ivanovic, the 13th seed, appears to be relishing her status as the new queen of Wimbledon.
The 21-year-old, who regularly tops polls of the sport´s most attractive players, has endured a miserable time since her world number one and French Open title breakthrough last year and is now ranked outside the top 10 for the first time in two years.
There had been a small sign of improvement in the first round here as Ivanovic saved two match points before eventually winning a three-set thriller against Lucie Hradecka.
Ivanovic showed her grasscourt credentials when she reached the semi-finals here in 2007 and she proved she has substance as well as style against Errani to set up a third round clash against Australia´s Sam Stosur.
After a quick exchange of breaks at the start of the first set, Errani, making only her second visit to Wimbledon, regained the lead with another break.
But to her credit, Ivanovic dug deep and broke Errani as she served for the set. With the momentum back in her direction, Ivanovic went for her shots with some abandon and broke again at 6-5 to take the first set.
The Serb was a far more dominant force now and broke twice early in the second set to take a 3-1 lead before closing out the match in one hour 17 minutes.
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