Williams continued her hot streak after winning last week's title in Miami, dispatching Italian Camila Giorgi 6-2, 6-3 in 1 hour, 22 minutes, firing nine aces en route to the triumph at Charleston.
The defending South Carolina champ defeated the Czech Republic's Lucie Safarova in last year's final.
The news wasn't as good for Stevens, however, who was dominated by fellow American Bethanie Mattek-Sands 6-2, 6-0 in a match that took less than an hour.
Also logging a surprise wins Tuesday were Switzerland's Stefanie Voegele, who bested seventh-seeded Spaniard Carla Suarez Navarro 6-2, 6-4, and American qualifier Jessica Pegula, who upended eighth-seeded German Mona Barthel 7-6 (7-4), 6-1.
Other Day 2 winners included 11th-seeded Romanian Sorana Cirstea, who won in a walkover, former Charleston champion Jelena Jankovic, No. 10 Julia Goerges of Germany, No. 12 American Varvara Lepchenko and American qualifier Vania King.
Fifteenth-seeded Sabine Lisicki of Germany and No. 16 Laura Robson also netted second-round victories.
Tuesday's first-round victors included New Zealand's Marina Erakovic, Croat Mirjana Lucic-Baroni and American Madison Keys.