Rouse made his feature film debut in David Gordon Green's George Washington, released in 2000, as a character's "cranky uncle." (George Washington was also Green's debut as a film Producer, film Director and screenwriter). Rouse was then cast in several more of David Gordon Green's films, including All the Real Girls in 2003, Pineapple Express in 2008, and The Sitter, opposite Jonah Hill, in 2011.
Rouse also appeared in the 2002 basketball-themed romantic comedy, Juwanna Mann; Ridley Scott's American Gangster and Joel Schumacher's The Number 23, both released in 2007; Pandorum as a chef who has gone crazy in 2009; and the 2010 Joaquin Phoenix mockumentary, I'm Still Here, directed by Casey Affleck. Rouse completed filming for the Seth Rogen film, The Green Hornet, in 2011, but his scenes were cut from the movie. He had experienced an uptick in roles during his later career, including parts in Being Flynn in 2012, Nature Calls in 2012, and Low Down in 2014.
Eddie Rouse died from liver failure at UCLA Medical Center in Santa Monica, California, on December 7, 2014, at the age of 60.
