On December 2, 2009, ABC confirmed that Ugly Betty would be moving to Wednesday nights after Christmas 2009, due to Eastwick's cancellation.

Daniel Eric Gold was promoted to the main cast as Matt Hartley, having appeared in a recurring capacity during Season 3.

Yaya DaCosta took over the recurring role of Nico Slater, who was played in the first season by Jowharah Jones.

In addition, the final season featured cameo appearances by singer Shakira, designer Brian Reyes, and drag queens Varla Jean Merman, Candi Shell, and Hedda Lettuce as themselves.

Walt Disney Studios Home Entertainment released Ugly Betty Season Four, subtitled "From Poncho, to Honcho", on August 17, 2010 in the United States and Canada.