Elsewhere in the draw, No.3 seed Aryna Sabalenka is in the top half with Stephens, and could potentially face her doubles partner and No.6 seed Elise Mertens in the quarterfinals.
The duo will play on the same side of the net on Sunday against Samantha Stosur and Zhang Shuai, as they attempt to pull off the Sunshine Double by winning the Miami Open.
In Charleston, each will get a first round bye, before squaring off against either a qualifier or Kristyna Pliskova, and Veronika Kudermetova or Kaia Kanepi, respectively.
No.7 seed Julia Goerges, runner-up to Bertens last year, could get another crack at the Dutchwoman in the semifinals, as she and No.7 seed Anastasija Sevastova headline the third quarter in Bertens’ half of the draw.
Goerges will face either a qualifier or American Taylor Townsend in her first match, while Sevastova will see either Jessica Pegula or Irina Khromacheva in the second round.
This week’s event will also see the return of hometown favorite and former World No.48 Shelby Rogers, who returns to her home tournament unranked following a year on the sidelines after knee surgery.
Rogers, a wildcard, faces Russia’s Evgeniya Rodina in the first round, with the winner a potential second round opponent for 2017 runner-up and current No.10 seed Jelena Ostapenko, or Johanna Larsson.
To see the full Charleston draw, click here.