Djokovic described soreness in his right wrist at the start of the week. The heavily taped wrist seemed to bother him more toward the end of the first set, and he served slower throughout the second.
"I just rest now. I cannot play tennis for some time. How long, I don't know," Djokovic said. "I'm going to rest and see when it can heal 100 percent, then I will be back on the court."
Federer is aiming for his first Monte Carolo win after losing three consecutive finals to eight-time champion Rafael Nadal from 2006-08.
The final Sunday will be the first all-Swiss affair since Marc Rosset beat Federer in Marseille in 2000, and the first meeting between Federer and Wawrinka for a title. Wawrinka, who trails Federer 13-1 overall, earned his only win against him here in 2009 in the third round.
"I was basically on my honeymoon. I married on Saturday and I came over here and played him like on Thursday," Federer said. "I know I have a good head-to-head against him. I don't read that much into it. He's a different caliber player now."
Federer's touch was inconsistent in his quarterfinal win against Jo-Wilfried Tsonga, but he was sharp against Djokovic. His casual drop shot surprised the Serb and drew loud cheers from the center-court crowd soaking up the Mediterranean sunshine.
"I feel like I have put in the performance to be there, gave myself the opportunity this week," Federer said. "Of course, I did see that Novak was struggling."
Federer broke for 6-5 when Djokovic netted a weak forehand. At the changeover, Djokovic nursed his wrist as he sat in his chair, looking stern-faced and pensive.
"It's unfortunate that when you're playing at this level against Roger, big tournament, that you are not able to play your game because something else is taking away all your energy and effort," Djokovic said. "This injury has been present for last 10 days, and I tried not to think or talk about it. I did everything I could really, I was on the medications every day, I was doing different therapies, injections."
Djokovic's first-serve speed dropped to 100 mph in the second set, and he had difficulty flexing his arm as he tried to return one Federer shot in the third game.
Federer secured successive breaks to take control. The fourth-ranked Federer raised both hands in the air after winning on his first match point, and Djokovic walked off looking despondent.
The third-ranked Wawrinka remains on course for his third title of the season, the fourth of his career on clay and his first in a Masters event.
"I think it's incredible that we are in the finals together, the same week we've been playing so well," said Federer, who got a wild-card invitation. "I know Spaniards have it, French guys have it, Americans might have it. But for us it's so rare. Last time was 14 years ago."
Wawrinka has six career titles, but lost his previous two Masters finals on clay — at Madrid last year and in Rome six years ago to Djokovic.