It was her first match in 10 months.
Vandeweghe, once ranked as high as ninth in the world, hadn't played a WTA singles match since falling in the first round of the China Open last September, having been slowed for much of 2018 by a nagging ankle injury that was followed by a foot injury.
"To think that five months ago I wasn't even walking, I'm just full of tons of emotions," the 27-year-old said after wrapping up the victory with an ace on match point in one hour and 23 minutes.
She hadn't won a singles match since June of 2018, and in her extended absence has dropped to 636th in the world.
"First and foremost, I was thinking of having fun," she said of her mindset coming into the tournament, for which she received a wild card.
While she missed the first edition of the tournament in San Jose last year, Vandeweghe was a two-time finalist in the event's previous incarnation in Stanford.
Vandeweghe earned a second-round meeting with second-seeded Aryna Sabalenka of Belarus.