The top-seeded Williams posted a 7-5, 6-3 decision over Vandeweghe at Stanford's Taube Family Tennis Stadium, repeating her victory of last year when she downed Marion Bartoli of France.
It was the 43rd career singles title for the 30-year-old American star.
Twenty-year-old countrywoman Vandeweghe was appearing in her first career final.
Aaron Carter is still in love with Hilary Duff
NBC reportedly holds celebs hostage to Jimmy Fallon's show