The 2017 US Open finalist was defeated by Konjuh 6-4, 6-2 in what was one of the Croatian's best displays since undergoing elbow surgery in 2017.

The only other seed to lose in the women's singles was Keys' compatriot Coco Gauff.

Anastasija Sevastova of Latvia won 1-6, 6-2, 6-3 against the 17-year-old.

Slovakia's Kristína Kučová came close to knocking out top seed and world number one Ashleigh Barty in a three-set match, however the Australian saved a match point to progress 6-3, 4-6, 7-5.

Romanian third seed Simona Halep also needed three sets to advance from her opening match at the Women's Tennis Association 1000 event.

Halep came from a set down to defeat France's Caroline Garcia 3-6, 6-4, 6-0.

Ukraine's fifth seed Elina Svitolina progressed in three sets as well, again coming from a set down to defeat American Shelby Rogers 3-6, 7-5, 6-3.

Seventh seed Aryna Sabalenka is another player into the round of 32, thanks to winning the final-set tiebreak against Bulgarian Tsvetana Pironkova.

Sabalenka eventually triumphed 0-6, 6-3, 7-6 (11-9).

Ninth seed Petra Kvitová of the Czech Republic comfortably defeated Alizé Cornet of France 6-0, 6-4, while reigning French Open champion Iga Świątek of Poland defeated unseeded Czech Barbora Krejčíková 6-4, 6-2.

In the men's singles round of 128, 2014 US Open champion Marin Čilić of Croatia progressed with a 6-2, 2-6, 6-4 win over Argentina's Federico Coria.

Bosnian Damir Džumhur prevailed in a tight match against former Wimbledon runner-up Kevin Anderson of South Africa 7-6 (8-6), 7-5 and home favourite Frances Tiafoe came from a set down to beat Italian Stefano Travaglia 5-7, 6-4, 6-2.