Anderson was born in Wahpeton, North Dakota. He is a graduate of the University of North Dakota in Grand Forks. During the 1970s, Sam taught drama at Antelope Valley College in Lancaster, California.
Anderson married in 1985 and is the father of twins. Sam holds advanced degrees in Theatre, American Literature and Creative Writing. He is also a member of the Mystery Writers of America.
Anderson is perhaps best known for his roles as mailroom supervisor Mr. Gorpley on Perfect Strangers, the lawyer Holland Manners on the first two seasons of Angel, the cardiologist Dr. Jack Kayson on the television series ER and as dentist Bernard on Lost, also as the assistant manager of the Hotel Royale in Star Trek: The Next Generation episode "The Royale", and as Mike Seaver's adversarial Principal DeWitt in Growing Pains. He was also one of the recurring actors on WKRP in Cincinnati who played various roles, including an immigration officer in the WKRP episode "The Americanization of Ivan" and a number of other episodes. Anderson has guest-starred in Season 8 of NCIS as Walter Carmichael, a middle school teacher whose classroom becomes a crime scene when one of his students is kidnapped.