After the war, Doohan started his acting career after being disheartened by the laughable quality of a radio drama, leading him to privately study Shakespeare, and with his first work a CBC radio show appearance on January 12, 1946. He took a drama class in Toronto, and later won a two-year scholarship to the Neighborhood Playhouse in New York City, where classmates included fellow Canadian Leslie Nielsen, Tony Randall and Richard Boone. For several years he would shuttle between Toronto and New York as work demanded. During this period Doohan appeared on some 4000 radio programs and 400 television programs, and earned a reputation for his versatility. In the mid-1950s he appeared as forest ranger "Timber Tom" (the northern counterpart of Buffalo Bob) in the Canadian version of Howdy Doody (coincidentally, fellow Canadian and Star Trek castmate William Shatner appeared simultaneously as Ranger Bill in the American original).
Doohan suffered from Parkinson's disease, diabetes, and lung fibrosis in later life. In 2004, he was diagnosed with Alzheimer's disease. On July 20, 2005, at 5:30 in the morning, he died at his home in Redmond, Washington with his wife Wende and long-time friend (and agent) Steve Stevens at his side. His agent identified the cause as pneumonia and Alzheimer's disease.