Clayton starred as one of the eight main characters in the Netflix original television series Sense8 that premiered on June 5, 2015. In Sense8 she played Nomi Marks, a San Francisco transgender female political Blogger and hacker. Clayton said that she was primarily interested in Sense8 because of the opportunity to play a transgender character that was written and directed by a transgender filmmaker, but that she was also a fan of science fiction and J. Michael Straczynski in particular.