Ellen Pompeo, who plays Dr. Meredith Grey will also guest star for seven episodes during the 21st season.
Her character's last appearance was on the show's 19th season in 2023 in the episode titled "I'll Follow the Sun."
Pompeo, who has starred in the show since the beginning, remains executive producer on the series.
Williams had an official send off in season 17 and was last seen making an appearance during the show's 19th season to help Pompeo's character move to Boston.
A new trailer teases more drama at Grey Sloan Memorial as Dr. Grey stirs up trouble and reunites with Dr. Avery.
Grey's Anatomy season 21 premieres September 26 on ABC.
Catch up on all the storylines and watch previous seasons of Grey's Anatomy on Hulu.
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