Wawrinka had caused the first major upset of the week when he battled Rafael Nadal throughout a thrilling quarter-final on Friday to send the seven-time Rome champion crashing out.
But despite a blistering start which saw Wawrinka race to a 3-0 lead in the opening set, the 30-year-old from Lausanne appeared to pay for his efforts late into the night at the Foro Italico.
Federer bounced back from losing the early break to break back twice on his way to sealing the first set 6-4.
Wawrinka was even more out of sorts in the second set, unforced errors steadily creeping into his game as Federer eased into his stride and reached a stage where he was able to pick his shots comfortably.
Federer, bidding for his maiden title in Rome having lost three finals — two to Nadal — earned three break points in the third game of the second set and won the game when Wawrinka attempted a wild half-volley from a tight angle which he netted.
Federer moved 3-1 up on his next service game and broke his fellow Swiss again for a 4-1 lead before wrapping up the set.
"I was happy with how I played, I was able to impose my game," Federer said.
"Basically rock solid from the moment I got my game down."
So far this year, it's one apiece between Djokovic and Federer, the former winning their last final at Indian Wells to make amends for Federer's win in Dubai.
Career-wise, Federer holds the advantage with 20 wins to Djokovic's 18, although the Serb has shown glimpses of brilliance this week and a variety of shots that put all of his rivals in trouble.
Having lost twice in Rome to Djokovic in the semifinals, Federer admitted he will have to be at his best on what will be their first clay final of the year.
"I've done fairly well against him in the past," added Federer.
"It's up to me to put in a really good performance."
Earlier, the Serbian swept clay court specialist David Ferrer aside in straight sets, breaking the Spaniard once in each set to secure his chance for a fourth crown in Rome.
Djokovic said he felt encouraged by a performance in which he held serve against "one of the best returners in the game" but admitted he had to dig his way out of trouble on occasion.
"I did face a couple of break points, especially in the second set, when maybe I was a bit fortunate to dig my way through and up, and play well enough to break him in both sets when it was most needed," said Djokovic.