In television, she is known for her leading roles in Freaks and Geeks (1999–2000), ER (2003–09), Bloodline (2015–17), and Dead to Me (2019–present), the latter of which earned her a nomination for the Primetime Emmy Award for Outstanding Lead Actress in a Comedy Series. She also guest starred in Mad Men (2013–15), for which she received a Primetime Emmy Award nomination.
In film, Cardellini is best known for her portrayal of Velma Dinkley in Scooby-Doo (2002) and its sequel Scooby-Doo 2: Monsters Unleashed (2004), and her supporting roles in Legally Blonde (2001), Brokeback Mountain (2005), Grandma's Boy (2006), Avengers: Age of Ultron (2015), Green Book, A Simple Favor (both 2018), and Avengers: Endgame (2019). She also starred in the drama Return (2011), earning an Independent Spirit Award for Best Female Lead nomination, the comedies Daddy's Home (2015) and Daddy's Home 2 (2017), and the horror film The Curse of La Llorona (2019).
