Novak Djokovic came from a set down to see off Stanislas Wawrinka in the final of the Rome Masters on Sunday.

The Serbian overcame some early struggles to defeat Wawrinka 4-6 6-3 6-3 and clinch his fourth career ATP Masters Series title.

The third seed at this claycourt event, Djokovic captured his third title this season and 10th career crown.

Just over a week ago, the Serb was forced to withdraw from his semi-final match with Roger Federer at the Monte Carlo Masters as a result of a throat problem.

But after battling through the illness en route to a hard-fought third-round victory over Igor Andreev, Djokovic barely had to work to reach Sunday's showdown with the unseeded Wawrinka.

"I didn't think that I'm going to play in the finals against a player who's unseeded, but obviously he deserved to be there," Djokovic said. "He showed his quality."

Djokovic won his quarter-final match on Friday when Nicolas Almagro withdrew due to a right wrist injury. One day later, Djokovic advanced again when Radek Stepanek bowed out due to an undisclosed illness.

It would be a much different story on Sunday for Djokovic, who dropped a crucial early break on his way to losing the first set.

"I knew that he's a difficult player to play against on this surface, because if you look at his history of the results, he made his best results on this surface," Djokovic said.

"So he's a specialist, and he didn't have anything to lose.

"I did what I needed to do. Even though I won in three sets, I think I'm happy in general with my performance in this tournament."

The reigning Australian Open champion converted a break in the second and two more in the third.

"I was always before him; I was pushing him," Wawrinka said.

"But I think it changed his game and he was coming more in at the net. In the second and the third set, he was serving very well, too."

Djokovic, who also has won Masters Series events at Indian Wells, Miami and Canada, improved to 4-2 all-time against Wawrinka, who became the first unseeded player to advance to this ATP Masters Series final since Felix Mantilla beat Federer in the 2003 championship.

On the season, the 20-year-old Djokovic improved to 25-5.

"Even this year, I showed great quality (on) hardcourt especially, but even on clay," Djokovic said. "I've been playing great. Out of what, 10 matches, I won nine, so it's great.

"I've been very satisfied so far, and that's what I will try to keep on doing. You know, being consistent on the major events with the results and that's the important thing if I really want to stay on the top."

An improbable finalist in a draw that had nine top-10 players participating, the 22-year-old Wawrinka was bidding for his second career title. But the Swiss player could not handle Djokovic's serve, winning just 23 per cent (16 of 71) of his return points.

"Of course a little bit disappointed because I lost today, but I lost against a very good player, the number three in the world," Wawrinka said.

"I didn't play a bad match. Of course, I can do a little better, so that's why I'm a little disappointed."

Overall, Wawrinka dropped to 1-5 all-time in finals, also finishing as a runner-up to Andy Murray at Doha in January.