Novak Djokovic and Alexander Zverev will square off Friday in a much-anticipated men's semifinal match in the 2021 U.S. Open at Arthur Ashe Stadium in New York. Djokovic is seeking his record 21st Grand Slam title, while Zverev is looking for his first after losing to Dominic Thiem in last year's final at Flushing Meadows. The German also beat Djokovic in the semifinals of the 2020 Tokyo Olympics on his way to the gold medal. Djokovic is 6-3 in all-time meetings, but the 34-year-old comes off a five-set quarterfinal match with Matteo Berrettini, while the 25-year-old Zverev got past Lloyd Harris in three. The match is scheduled to begin at 7 p.m. ET.

Caesars Sportsbook lists Djokovic as the -225 favorite (risk $225 to win $100) in its latest Djokovic vs. Zverev odds, while Zverev is the +175 underdog. The over-under for total games is set at 38.5. Before locking in any Zverev vs. Djokovic 2021 U.S. Open men's semifinals picks, you need to see what expert Sean Calvert has to say.

Calvert is the renowned handicapper who called Stan Wawrinka winning the 2014 Australian Open at 60-1, the last Australian title won by someone other than Djokovic or Roger Federer. In 2019, Calvert took down a huge score on Dominic Thiem winning Indian Wells at 80-1. 

And earlier in 2021, he nailed both of his bets for the Wimbledon men's singles final: Djokovic to beat Matteo Berrettini three sets to one (+275) and Djokovic to win and both players to win a set (+130). Anyone following his picks is way up.

Now, Calvert has been digging deep into the latest 2021 U.S. Open odds and released his coveted best bet for Zverev vs. Djokovic. He's only sharing his expert U.S. Open picks and analysis at SportsLine.

Novak Djokovic vs. Alexander Zverev preview

The Olympic semifinal was an unusual misstep for Djokovic, who won the first set 6-1 and was up 3-2 in the second. But he won just one more game, and Zverev should bring confidence into this matchup after an emphatic gold-medal victory against Russian Karen Khachonov. The German has won 16 straight matches since Wimbledon and should be fresher than his older counterpart. The Serb played in the last semifinal match and needed almost three hours to get past his Italian foe. But Djokovic is as fit as they come and will be focused on the task.

The pressure will be on Djokovic as he seeks to become the first player since Rod Laver in 1969 to win a calendar-year Grand Slam, but he has seen a lot of that over the years. Zverev will be facing his own mental hurdles as the 24-year-old tries to get back to the final. He faced Dominic Thiem for the Open title last year but coughed up a two-set lead and lost on a fifth-set tie-break. Djokovic had been disqualified earlier in the tournament, and Rafael Nadal and Roger Federer were also absent from that event. The question is, will the German use that loss as motivation, or will he have it in the back of his mind in a match of this caliber? 

How to make Djokovic vs. Zverev picks

Calvert has broken down the latest U.S. Open men's odds and released a plus-money best bet for this semifinal matchup. Calvert's expert U.S. Open picks are available only at SportsLine.

Who wins Zverev vs. Djokovic in the 2021 U.S. Open men's semifinal? And what best bet do you need to be all over? Visit SportsLine now to see Sean Calvert's best bets for Zverev vs. Djokovic, all from the famed tennis handicapper who called Wawrinka winning the 2014 Australian Open at 60-1, and find out.