Males:
Jared Leto for Chapter 27
Females:
Charlize Theron for Monster
I’m sure there are tons more, but what actors/actresses who are known for their good looks intentionally tried to become ugly for a role?
Boris Karloff was rather handsome, without the neck bolts.
Farrah Fawcett was a mess by the end of The Burning Bed, at least according to the promos.
Nicole Kidman put on an ugly nose to play Virginia Woolf (and won an Oscar i nthe process).
You’ve already named the best example. Theron’s transformation was amazing. She was willing to go beyond “Hollywood ugly”.
Pat Moran in Desperate Living
Carol Kane in The Princess Bride and Addams Family Values
Eric Stoltz in Mask
Mel Gibson in The Man Without a Face
Emma Thompson in Nanny McFee.
Christian Bale in The Machinist.
Josh Brolin in Jonah Hex
Aaron Eckhart in The Dark Knight(for some of the movie, anyway)
Heath Ledger in the Dark Knight
Angelica Huston in about half of her movies.
Vicky Lawrence for Mama’s Family.
Cameron Diaz in Being John Malkovich
Sandra Bullock in Babe.
Hilary Swank in Seabiscuit.
And The Fighter.
And yet she insisted that it “not be about the makeup.” And she succeeded at that.
Tom Cruise and his fatsuit in Tropic Thunder.
Ana Maria Orozco’s rise to fame was explicitly for becoming “ugly.”
Donna Murphy in the Broadway musical “Passion”
Javier Bardem in No country for old men