The top-seeded defending champ shook off a sluggish first set to record a 3-6, 6-0, 6-2 victory over ninth-seeded Jankovic, taking a tournament crown for the second straight week following her triumph in Miami.
Williams racked up her 22nd consecutive clay court match win -- including 15 straight in Charleston, where she claimed her third overall career title.
She advanced after beating her older sister Venus in the semifinals.
Jankovic, meanwhile, had reeled off 14 wins in her previous 16 matches coming into Sunday's final. She fell short in her bid for a 14th career title and second in Charleston.