The 39-year old lost to compatriot Coco Gauff in the first round of the Australian open, before losing at the same stage last week in Acapulco.
Venus Williams faced Slovakian qualifier Anna Karolina Schmiedlova a first-round encounter in Monterrey, as she was looking to join sister Serena as the only women to win a match across four decades. However, it was the Slovak who stunned the capacity crowd, rallying from a set down to win 4-6 6-3 6-2.
Although the American raced to a 5-1 lead and quickly claimed the first set, it was Schmiedlova who overcame her nervous start and dictated play for the rest of the match. Some errant play and double faults from Williams gave Schmiedlova her much needed break, and she never looked back each time. The World No.199 converted on her first match point and won the match after two and a half hours of play.
Schmiedlova next faces ninth seed Marie Bouzkova, who cruised past Kristina Kucova 6-4 6-2 in an hour and 41 minutes.
Sixth-seeded Swede Rebecca Peterson needed two and a half hours to battle past Ukraine's Kateryna Kozlova 3-6 7-6(1) 6-4. Belarusian Olga Govortsova also required three sets to advance, defeating American Caroline Dolehide 3-6 6-2 6-1.
Eight seed Yafan Wang beat Spaniard Lara Arruabarrena 6-4 6-4 in an hour and 26 minutes, while Aussie Astra Sharma defeated Serbian Nina Stojanovic 6-4 6-4 to advance to the second round.
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