Argentine Del Potro overpowered Richard Gasquet 6-2 6-2 to reach his fifth final of the year while world number one Federer met more resistance before beating Paul-Henri Mathieu 7-5 6-4.
Federer has spoiled what has otherwise been an excellent year for Del Potro, winning all six of his meetings against the Argentine on a mixture of clay, grass and hard courts.
The most recent of those was their astonishing Olympic semi-final at Wimbledon where Federer won a 36-game final set.
Del Potro, who claimed his third title of the year in Vienna last week, also lost to Federer in the quarter-finals of the Australian and French Opens, the Rotterdam final, the Indian Wells quarter-final and the Dubai semi-finals.
Overall, Federer has won 13 out of 15 meetings with Del Potro whose only wins over the Swiss were at the U.S Open final in 2009 and at the World Tour Finals the same year.
"You have to hit winners all the time and see if you have a chance to win, there are very few players who can beat him," Del Potro told reporters.
"This year, I have lost to him six times already, I was very close at the Olympics and I was ahead at the French open."
"It will give me a chance to measure myself against him and see how far I have come."
"The important thing is to keep getting closer to the top five," added Del Potro, who has edged his way back towards the top despite a series of injuries including a wrist problem which forced him to miss most of the 2010 season.
Gasquet provided some resistance for the first four games which all went with serve.
Del Potro then won the next four games to take the first set which he wrapped up with his third ace of the match.
Both players lost their opening serve in the second set and, although Del Potro's serve was not at its best, he was still far too powerful for the Frenchman, running out an easy winner to win his eighth match in a row.
Federer did not have to face one break point against Mathieu, converting two of the four that came his way to ease into the final of his hometown where he will be looking for a sixth title on Sunday.
In Valencia, local favourite and top seed David Ferrer will meet Ukrainian Alexandr Dolgopolov in the final after beating unseeded Croat Ivan Dodig 6-4 6-7 6-1.
The world number five, who has a shot at his sixth title of the season in Sunday's showpiece, finally ground down his opponent after two hours and 42 minutes.
"Dodig served very well throughout and made it very difficult for me," the 2008 and 2010 Valencia champion Ferrer was quoted as saying on the tournament website.
After losing a second-set tiebreak, Ferrer recovered to ease past his tiring opponent in the third.
"I tried to forget about what happened in the second set, I knew I was playing well," said the Spaniard. "I knew that if I was able to break his serve I would be able to win."
Ferrer has already qualified for next month's World Tour Finals in London along with Novak Djokovic, Roger Federer, Andy Murray, Tomas Berdych and Juan Martin del Potro.
Former world number one Rafael Nadal has withdrawn with his long-standing knee injury and there are two places still up for grabs.
Dolgopolov, who knocked out defending champion Marcel Granollers in the quarter-finals on Friday, swept aside Valencia debutant Juergen Melzer of Austria 6-4 6-2 in the second semi.
ATP Basel semi-final results
1-Roger Federer (Switzerland) beat Paul-Henri Mathieu (France) 7-5 6-4
2-Juan Martin Del Potro (Argentina) beat 3-Richard Gasquet (France) 6-2 6-2
ATP Valencia semi-final results
1-David Ferrer (Spain) beat Ivan Dodig (Croatia) 6-4 6-7(5) 6-1
Alexandr Dolgopolov (Ukraine) beat Jurgen Melzer (Austria) 6-4 6-2
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