Sanderson is anything but a hick, however. After a rebellious youth and a stretch in the army, he graduated from Memphis State University and then went on to its law school. Sanderson opted to move to NYC to pursue an acting career rather than practice law. He found work off-Broadway where he appeared in over thirty stage productions. By the early 1980s, Sanderson was working in movies and on TV. He is remembered as the young uncle to Loretta Lynn (Sissy Spacek) in Michael Apted's "Coal Miner's Daughter" (1980) and, teamed again with Spacek, as Calvin in Jack Fisk's "Raggedy Man" (1981). Sanderson contributed a moving vignette as a prematurely aging designer who harbors the runaway android (Darryl Hannah) in Ridley Scott's "Blade Runner" (1982). He has also had roles in other high profile features like Hal Needham's "City Heat" (1984), Joe Johnston's "The Rocketeer" (1991) and Joel Schumacher's "The Client" (1994) followed.
On TV, Sanderson offered strong turns as a convict trying to help youth offenders stay out of prison on "Scared Straight: Another Story" (CBS, 1980) and as Tommy Lee Jones' cell mate in "The Executioner's Song" (NBC, 1982). That same year, he made a guest appearance as a local hayseed on the CBS sitcom "Newhart" and, based on positive reaction, was asked to join the cast in a recurring role. As Larry, he would enter the inn with his two brothers and utter, "Hello, my name is Larry. This is my brother Darryl, and my other brother Darryl." No one was sure what made this funny, but the audience loved it and, at one point, there was even talk of a spin-off series. In 1989, Sanderson was cast as Lippy Jones in the Western miniseries "Lonesome Dove" (CBS), a role he reprised in 1993's "Return to Lonesome Dove". He also won critical praise for his performance as a sadistic inmate in the Civil War-era prison camp drama "Andersonville" (TNT, 1996), directed by John Frankenheimer. Sanderson's distinctive voice began to be used in animated series in the 1990s, including "Santo Bugito" (CBS, 1995), set in a sleepy Southwestern town.