Raonic, from Thornhill, Ont., lost to del Potro in the semifinals of the Indian Wells Masters earlier this month.
The American world number 17 hit 39 winners to seal a 6-1 7-6 (7-2) victory in one hour 22 minutes.
The 20-year-old German will now set his sights on collecting his seventh career ATP Tour title and third Masters 1000 crown when he faces 14th-seed Isner in Sunday's final.
But on Friday, the 32-year-old Isner took the racquet out of the World No. 6's hands with outlandish serving and free-swinging play from the baseline, intertwined with effective trips to the net with sweetly placed drop volleys.Del Potro was unable to earn a break point against Isner, or even get to deuce. In those games, he has only faced a single break point.
After a drab first set by his standards, del Potro was able to start the second set well with an opening hold, and eventually eased into the match with some solid form; he could do little to try and break down Isner however, who remained solid on serve throughout the set.More news: Foreign Minister Bishop 'not considering' Australia World Cup boycott
"I think I'm playing OK", he said.
"I was down in the tiebreak and I was like, I'm losing anyway I might as well be aggressive. He was better than me, and he deserved to win".
"We both played well, the difference was perhaps that I just played better in the tie-breaks". He's playing well so far this week, so it's going to be a hard match. "I'm going to be very tough to beat.", he said. The final, against Pablo Carreno Busta or Alexander Zverev, will be at 1 p.m. Sunday (ESPN2). You know, he's coming into this match winning so many matches.
An exhausted Del Potro said he is looking forward to some much-needed time away from tennis before deciding on when to play next.
Elsewhere in the Miami Open, world No. 5 Alexander Zverev defeated Croatia's Borna Coric in straight sets Thursday to reach the semifinals.
Isner is the first USA player since Andy Roddick in 2010 to lift the Miami title. "And I'm so happy to be doing it here". Despite that, the two have always been put on a display of high-quality tennis, with their match in Miami a year ago the most entertaining. Their first match came in 2016 in the first round of the Shanghai Masters when Zverev put in a dominant performance to defeat Isner 6-4 6-2. "I made some winners; made some backhand winners finally in the match and found my rhythm".