The 47-year-old moviemaker has undergone a sex change operation and now goes by the name Lana.
With her hair in pink dreadlocks, Wachowski introduced herself for the first time as a woman in a behind-the-scenes trailer for the new drama, saying, "Hi, I'm Lana."
The Matrix director was previously married to Thea Bloom. They divorced in 2002 after nine years of marriage.
Wachowski is not the first celebrity to come out as transgender in recent months - Cher's daughter Chastity is now known as Chaz Bono, Against Me! singer Tom Gabel recently became Laura Jane Grace, and Warren Beatty and Annette Bening's eldest child, daughter Kathleen, is formally called Steven Ira.