Williams’ title defence came six years after Kim Clijsters completed her double.
Vandeweghe, ranked 120 but set for a rise into the top 75, was bidding for history in hopes of becoming the second lucky loser from qualifying rounds to win a WTA title. The Californian got into the field after another player withdrew before the start.
Williams has two trophies in as many weeks after winning Wimbledon last weekend, then flying to northern California to shift onto the hardcourts. The world number four now owns 43 career titles, the same number as her sister Venus.
Williams also has four wins in 2012, putting her joint leader in that category alongside world number one Victoria Azarenka.
Also writing her name into the history books is Sara Errani, the Italian who won the Palermo title also on Sunday.
She becomes the first Italian ever to win four WTA titles in a season.
Errani, who had already won claycourt events at Acapulco, Barcelona and Budapest this year, routed eighth seed Barbora Zahlavova Strycova in the final, 6-1, 6-3.
“It wasn’t easy like the score looks – Barbora was playing very aggressively and it was tough for me,” said French Open runner-up Errani.
The previous record for most WTA titles in a season for an Italian came just last year, as Errani’s best friend and doubles partner, Roberta Vinci, won three, at Barcelona, ‘s-Hertogenbosch and Budapest.
“I wasn’t thinking about the record today, but I’m very happy to have the record – to win four tournaments in a season is incredible for me,” Errani said.
“It’s a magic period for me. This year I’ve played some fantastic tennis on clay, losing only a few matches, but I really want to improve my results on hard and grass.