The last time del Potro and Federer played was a year ago in the Basel final where the latter won 6-7 (5-7), 6-4, 6-3.
The 2009 US Open victor, however, faces a daunting task against defending champion and world number one Federer, who improved to 17-0 for the year after rallying past Borna Coric.
The thrilling victory - lasting nearly three hours - secured a maiden Masters 1000 title for world number eight Del Potro and just his seventh win in 25 attempts against Federer. Federer comes into the final on the back of a hard fought come-from-behind win against Borna Coric in the semifinals while Del Potro had an easier time against Milos Raonic.
But Federer's cunning saw him work back into the match in the second set, winning a tiebreak and taking it to a decider. He started in ideal fashion by claiming the first set, but if he hoped taking an early lead would get the crowd on his side, he was wrong.
Federer, along with Novak Djokovic, have won 5 Indian Wells Masters Title.
Roger Federer was on the ropes, down two breaks in the second set and another one in the third. In the quarterfinals, No. 37 Philipp Kohlschreiber effectively used his drop shot to throw off Del Potro, who had to again come from behind to earn the victory. Federer reached match point not once, not twice, but three times.
36-year-old Swiss superstar Federer was into the final in Indian Wells for the fourth straight time, having missed the event in 2016.
After his win, del Potro, who has had three operations on his wrist in the last four years, gave the reason behind his victory.
"This is the toughest I've been pushed this year, more than the Australian Open final."Federer struggled to find rhythm in the earlier stages of the match.
"I was aggressive and I was pushing him to the limits, but at the end he was better player", Coric said. Del Potro saved that too, with a good serve.
This will be Del Potro's second appearance in the final. Del Potro's best run against Fed was a three-match win-streak spanning the 2012 and 2013 seasons. With these 1000 points, Juan Martin will return into the Top 6 tomorrow for the first time since February 2014, and he is ready for more success in the rest of the season if he keeps this level of tennis. Federer still holds a sizable advantage in the win/loss column, taking home 18 of their 25 contests.
"I love to play against him", the Argentinian said.
The standard wasn't always ideal - both players made uncharacteristic unforced errors as Del Potro's forehand failed him and Federer's backhand didn't come to the party.
Federer said the defeat would hurt, but he took plenty of positives from the tournament as his record slipped to 17-1 this year.