Two days after Federer was surprisingly taken to five sets by Tomas Berdych, the 13-times grand slam winner wasted little time in thrashing the eighth seed in just 80 minutes.
The 20-year-old del Potro, considered to be one of the rising players of the game having won four tournaments last year and the Auckland event earlier this month, had no answer to the Swiss.
Such was Federer´s dominance, del Potro won just eight points in the second set and six in the third as the 27-year-old Federer advanced to his 19th successive grand slam semifinal.
Earlier, Roddick ended Novak Djokovic´s defence of his Australian Open title prematurely as the Serb was forced to retire from his quarterfinal.
Roddick had been leading 6-7, 6-4, 6-2, 2-1 when a visibly distressed Djokovic said he could no longer continue.
The 21-year-old had called a medical time out after the third game of the third set, when he had held serve to take a 2-1 lead, but looked exhausted when play resumed and lost the next five games.
Roddick held four break points in the first game of the fourth set and while Djokovic battled back to hold serve it may have sapped any semblance of energy he had left, as the seventh seed won the next game then broke him to love.
The third-seeded Djokovic then walked off court, consulted the doctor and told chair umpire Carlos Ramos of Portugal "no more," before he went to congratulate Roddick, who has now advanced to his fourth Melbourne Park semifinal.
Meanwhile, Dinara Safina charged into the women’s singles semifinals with a 6-4, 4-6, 6-4 win over a brave Jelena Dokic.
Safina ended Dokic´s emotionally-charged run at Melbourne Park to reach her third grand slam semifinal in eight months and stay on course to emulate her big brother Marat Safin by winning the Australian Open.
Tuesday´s see-sawing quarterfinal was still in the balance after the pair split the first two sets and were level at 4-4 in the third when Safina got the decisive break off a Dokic error then served out the match.
Safina, ranked three in the world, plays her fellow Russian Vera Zvonareva who won 11 games in a row to demolish Marion Bartoli 6-3, 6-0 and enter the first grand slam semifinals of her career.
Frenchwoman Bartoli made a bright enough start to open up a 3-1 lead in the first set, but she was unable to cope with the Russian´s power when she suddenly raised her game.
Seventh seed Zvonareva went on to register an easy victory in just 68 minutes with a performance that even she was unable to explain.
"I don´t know what happened," Zvonareva said.
"Marion was playing really well in the beginning and I made a few unforced errors, so that´s why I think I was down 3-1. Then I was able to cut down on my unforced errors and I was able to keep a good level of play throughout the whole match."
Despite being a consistent top-10 player, Zvonareva has a modest record at the grand slams and the only time previous time she had made it past the fourth round was at the 2003 French Open, when she made the quarterfinals.
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