Federer, who always looked in control, won 6-4, 6-3, 6-2 on a sun-drenched Rod Laver Arena and will next face either long-time rival Rafael Nadal or Czech Tomas Berdych.
In a rematch of the 2009 US Open final won by the Argentine, the third seed started in ominous fashion, unveiling his full repertoire of strokes and breaking del Potro at his first opportunity.
The tall Argentine, seeded 11th, settled and forced a break of his own in the seventh game, but a double-fault cost him the opener.
An exquisite backhand down the line gave Federer another break and a 3-1 lead in the second set, and he moved two sets clear after a tough ninth game in which he was forced to save four break points.
But that game proved a key missed opportunity for del Potro as he was again broken early in the third set, and an untroubled Federer broke again on his way to taking it 6-2.
‘I’m very happy,’ Federer said. ‘I thought it was a great match. It was tough with the sun and shade creeping across the court but I thought we did well. I thought it was a high-quality match.’
Federer said he was aware of the dangers posed by the 6ft 6ins (198 cm) del Potro but said he was ‘able to manoeuvre him around’ the court.
He said he would probably tune in to watch the later semi-final between Nadal and Berdych, even though he knew the games of both well.
‘There are no secrets out there but I will still enjoy it. I love good tennis,’ he said.
Victory for 16-time grand slam winner Federer, who has not yet dropped a set — although he had a walkover in the second round — means he advances to his 30th grand slam semi-final, just one behind Jimmy Connors on the all-time list.
The Swiss is chasing his first major since his Australian Open triumph in 2010 after failing to win a grand slam last year for the first time since he captured his first, at Wimbledon in 2003.
Del Potro last year made a rapid comeback from a wrist injury that kept him out for most of 2010, improving from a low of 485 in the rankings in January 2011 to a year-end ranking of 11.
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