Mihaela Buzarnescu's Silicon Valley Classic title defence ended at the first hurdle, while CoCo Vandeweghe made her first appearance in 10 months.
Defending champion Buzarnescu was a shock casualty on Monday, the Romanian eliminated by Daria Kasatkina 6-2 6-2 in San Jose.
Two-time grand slam semi-finalist Vandeweghe, meanwhile, enjoyed a winning return against Marie Bouzkova 6-2 6-4 at the WTA Premier tournament.
Recurring ankle and foot injuries had left former world number nine Vandeweghe sidelined since the 2018 China Open in September, however, she celebrated a successful comeback.
"It wasn't easy. To think, five months ago, I wasn't even walking to be here, playing, in my first...match of the year, I'm just full of emotions," said Vandeweghe, who also snapped a nine-match losing streak in singles, dating back to the Libema Open in June last year.
Awaiting American Vandeweghe – San Jose runner-up in 2012 and 2017 – in the next round is second seed Aryna Sabalenka.
Carla Suarez Navarro and last year's runner-up Maria Sakkari also progressed to the second round with respective wins over Magda Linette (6-3 6-3) and Ekaterina Alexandrova (6-1 6-4).
Kristie Ahn outlasted Ajla Tomljanovic 6-3 4-6 6-4 to set up a clash with third seed Elise Mertens and Mayo Hibi prevailed 6-2 3-6 7-6 (7-3) against Timea Babos.
At the Citi Open, former Wimbledon finalist Bouchard lost to American Lauren Davis 6-1 6-2 in Washington.
Next up is third seed Sofia Kenin, who was too good for Jennifer Brady 6-2 6-4 earlier on Monday.
Lesia Tsurenko – the fifth seed – eased past Wang Yafan 6-3 6-2, Christina McHale topped Anastasia Pavlyuchenkova 6-2 4-6 7-5, Nao Hibino lost 6-1 6-1 to Anna Kalinskaya, Jessica Pegula beat sixth seed Katerina Siniakova 6-4 6-3, Varvara Gracheva defeated Anna Blinkova 6-2 5-7 6-2 and Iga Swiatek saw off Ons Jabeur 4-6 6-4 6-4.