Djokovic is potentially looking at a third Grand Slam win in 2016, which would be the second time he has accomplished such a feat in his illustrious career. However, that looks to be a difficult task, with Wawrinka coming off consecutive wins over two of the strongest opponents in the tournament.
Take a look below at the schedule for Sunday's final, along with a breakdown of the matchup. See the path each player took to reach this position with a full tournament bracket, courtesy of ESPN.com.
To say these two have history might be an understatement, as Djokovic and Wawrinka have met 23 times in their professional careers.
Yet it's been Djokovic who owns this matchup. He is 19-4 against Wawrinka, having beaten the Swiss national in both of the U.S. Open fixtures the two played. While Djokovic entered this tournament with lingering left-wrist and right-arm issues, he has had the benefit of a fabulous draw.
Djokovic has seen two opponents retire along with a walkover match thus far, resulting in the Serbian dropping only one set. That came in his semifinal bout with Gael Monfils, where he was still in total control throughout the match. Wawrinka, on the other hand, has battled through two straight matches with quality opponents.
In the quarterfinals, it was the resurgent Juan Martin del Potro who finally fell after a four-set showdown with Wawrinka. Then he put on a show by storming back to win three straight sets after Kei Nishikori got out to a one-set lead. His recent play should make Wawrinka feel confident, as he has also won 10 straight tournament finals, per ESPN's Greg Garber.
Wawrinka is still well aware of the magnitude of the challenge ahead, per Garber.
"I'm really excited," Wawrinka said in his on-court interview. "I watched the final so many times here. Roger [Federer] and Novak are great champions. To play in the final against him is going to be special.
"Hopefully, I'm going to be ready."
Wawrinka does have some momentum going for him, but the circumstances of this match seem to favor his opposition.
Djokovic is much more fresh at this point than Wawrinka, and he also holds a steady advantage in comfort on hard surfaces. Djokovic is 33-2 this season on such surfaces with an 84 percent career-winning rate. This outweighs Wawrinka's 19-6 mark and 63 percent rate.
In this tournament, Djokovic also holds an edge in return points and unforced errors, which is crucial in a matchup where both players rack up points when holding serve. Djokovic has yet to exceed 30 unforced errors in a match, while Wawrinka has passed that number every time he has taken the court, and he committed more than 40 three times.
That comparison is skewed due to disparity in games played between Djokovic and Wawrinka, but another telling statistic in that regard is Djokovic's ability in the return game. He is averaging about one more return game win per match than Wawrinka.
This makes it difficult for Wawrinka to get up on Djokovic early. Wawrinka is 28-2 this year when winning the first set, and 4-10 when dropping the initial set. By contrast, Djokovic is 45-0 when taking the first set but a solid 6-5 when losing the opening frame. So even if Wawrinka can get an early lead, Djokovic is still in a strong position to win the match.
There is also an experience aspect, as Djokovic is one of the most decorated players ever, per ESPN:
This is the first U.S. Open final for Wawrinka, while Djokovic has graced this stage six times with two wins.
Wawrinka has struggled mightily against Djokovic throughout his career. With Djokovic's health issues being alleviated with a light schedule and the numerous factors working in his favor, there seems to be little reason to believe Wawrinka can overcome Djokovic on Sunday.