Earl Hammond began acting in radio at the age of 7 and continued working in that venue throughout his life. In the 1940s, he had a regular role as a young lawyer on a radio soap opera. From 1974 to 1982, he acted on the CBS Radio Mystery Theater, appearing in 189 episodes -- more than 12% of the entire run of the 1,399 episodes of that radio series.

Hammond started his television career in the early 1950s, his first major role being as a regular called Sergeant Lane on the DuMont police drama "Inside Detective" (aka "Rocky King Detective," starring Roscoe Karns). At the same time, he also was the first of three actors to portray the title character in the short-lived ABC TV science-fiction adventure series Buck Rogers, which ran from April 15, 1950, to January 30, 1951. In the mid-1950s, he had a major role in the daily/noontime CBS television soap opera Valiant Lady as Hal Soames, the married love interest of the widowed title character.

Hammond was perhaps best remembered for providing the voices of Mumm-Ra, Jaga, and other characters on the 1980s animated TV series ThunderCats, and for being the voice of villain Mon*Star on the 1980s animated TV series Silverhawks. He also was the voice of the Transformers villain Megatron in a series of children's read-along books.

In 1994, Hammond was selected from among several hundred actors who auditioned to be the voice of Pope John Paul II on the audiotape version of the Random House book Crossing the Threshold of Hope. The publisher said the pope personally selected Hammond.