Karlovic served well and charged the net with his enormous wingspan, making it difficult for Hewitt to pass. The Australian cracked under the constant pressure, misfiring on two ground-strokes to lose his serve and give Karlovic a 5-4 lead in the final set.
One point in the final game underscored the mismatch in size. Hewitt hit a topspin lob, a shot that frequently bails him out of trouble, but Karlovic reached up and slammed it for a winner.
Two points later, Karlovic had his stunning victory. He finished with 18 aces and 41 service winners, and won despite breaking serve just twice.
Last year, another unknown Croat, Mario Ancic, upset Federer in the first round. Goran Ivanisevic of Croatia won the 2001 title.
"Goran, he was always my idol," Karlovic said.
"He gave me congratulations."
Hewitt dropped only two sets en route to the title last year, but his game has slipped in 2003, and he'll fall to at least fourth in the next rankings. The Australian lost the No. 1 ranking to Andre Agassi last week and has failed to reach a Grand Slam quarterfinal this year. He was beaten in the fourth round at the Australian Open by Younes El Aynaoui and in the third round by Tommy Robredo at the French Open.
Hewitt's latest loss opens up that quarter of the draw for Roddick, who never lost serve and needed only 80 minutes to beat Sanguinetti.
The 20-year-old Roddick began working this month with Agassi's former coach, Brad Gilbert. The pairing quickly paid off with Roddick's first grass-court title at Queen's Club, and with perhaps the most formidable serve in tennis, he's touted as one of the Wimbledon favorites.
"Roddick is playing the best tennis of his life, maybe, at the moment," three-time Wimbledon champion Boris Becker said.
Williams, seeded fourth, beat Stanislava Hrozenska of Slovakia 6-2, 6-2 in 50 minutes. Davenport, seeded fifth, defeated Australia's Samantha Stosur 7-6 (7-3), 7-5. American Samantha Reeves eliminated No. 25 Anna Pistolesi of Israel 6-4, 6-4.
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