Huston received Academy Award nominations for Enemies, A Love Story (1989) and The Grifters (1990), for Best Supporting Actress and Best Actress, respectively, BAFTA nominations for Best Supporting Actress for the Woody Allen films Crimes and Misdemeanors (1989) and Manhattan Murder Mystery (1993) and Golden Globe nominations for Best Actress β Motion Picture Comedy or Musical for starring as Morticia Addams in The Addams Family (1991) and its sequel Addams Family Values (1993). She also received acclaim for her portrayal of the Grand High Witch in Roald Dahl's film adaptation The Witches (1990). Huston has frequently worked with director Wes Anderson, starring in The Royal Tenenbaums (2001), The Life Aquatic with Steve Zissou (2004) and The Darjeeling Limited (2007). Her other notable credits include The Dead (1987), Ever After (1998), Buffalo '66 (1998), Daddy Day Care (2003), 50/50 (2011) and John Wick: Chapter 3 β Parabellum (2019). She has lent her voice to several animated films, mainly the Tinker Bell franchise (2008β2015).
On television, Huston has had recurring roles on Huff (2006), Medium (2008β2009), and Transparent (2015β2016). She won a Gracie Award for her portrayal of Eileen Rand on Smash (2012β2013). Huston made her directorial debut with the film Bastard Out of Carolina (1996). This was followed by Agnes Browne (1999), in which she also starred. She has written the memoirs A Story Lately Told (2013) and Watch Me (2014).