2022 U.S. Open tennis odds: With top two seeds ousted, Nick Kyrgios now favored to win first Grand Slam tournament

With Russia's Daniil Medvedev losing Sunday night and Spain's Rafael Nadal losing Monday, the 2022 U.S. Open is the first where both top-2 men's seeds failed to reach the quarterfinals since 2000 when No. 1 seed Andre Agassi lost in the second round and No. 2 Gustavo Kuerten fell in the first. The new tournament betting favorite at Caesars Sportsbook is Aussie Nick Kyrgios, the No. 23 seed, at +160.

The 27-year-old Kyrgios is as talented as just about anyone on the ATP Tour but tends to let his temper get the best of him. That's partly why he has won just seven singles titles in his career and none in a Grand Slam. He was a runner-up at Wimbledon this summer, though, losing to No. 1 Novak Djokovic in four sets.

Kyrgios had never been past the third round of the U.S. Open but knocked off Medvedev in four sets Sunday to reach the quarterfinals tonight against No. 27 Karen Khachanov of Russia. With the upset of Medvedev, Kyrgios became the first player to beat a world No. 1 twice in the same year since Pat Cash in 1987. However, U.S. Open officials hit Kyrgios with a $4,000 fine for an audible obscenity during the match. It marked the third time he has been fined in this tournament, including once in doubles.

For the quarters, Kyrgios is a -500 favorite with Khachanov at +340. The two have split two previous career meetings and haven't played since the 2020 Australian Open.

The highest-seeded player remaining on the men's side is No. 3 Carlos Alcaraz of Spain, and he's a +220 second favorite to win his first Slam – Alcaraz and Kyrgios could only meet in the final. Alcaraz faces No. 11 Jannik Sinner of Italy in their quarterfinal match Wednesday.

American 24-year-old Frances Tiafoe, who got the biggest win of his career by knocking out Nadal on Monday, is +1400 to win the U.S. Open and faces No. 9 Andrey Rublev of Russia on Wednesday. Tiafoe is in the Alcaraz/Sinner half of the draw. It marked the first time since Wimbledon 2017 that Nadal lost before the quarterfinal stage of a Grand Slam. Tiafoe joined Andy Roddick and James Blake as the only Americans to defeat Nadal in a major.

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