See main article: article and 2021 MUSC Health Women's Open.
Hailey Baptiste and Caty McNally won the second 2021 Charleston Open, billed as the MUSC Health Women's Open, defeating Ellen Perez and Storm Sanders in the final, 6–7(4–7), 6–4, [10–6]. This was Baptiste's first WTA doubles title.
The 50th playing of the tournament occurred immediately after the 49th playing in 2021. This featured consecutive events, with the 2021 Volvo Car Open being the first. The second Charleston tournament was organised with a single-year license in 2021.[1]