Don's first jump into the entertainment business was a ventriloquist. He and his dummy, Danny, were paid to perform at various parties and events around town. After graduating high school, Don went to New York City but wound up moving back home after a few weeks. He enrolled in West Virginia University (WVU).
At the age of 19, Don enrolled in the army and was transferred to a special service unit to entertain the troops during World War II. Don eventually got tired of his ventriloquist act, left his dummy on the beach and moved on to comedy. When the war was over, Don returned to WVU and graduated. Don got married and he and his wife moved back up to New York.
With the help of the connections he made in the service, Don was able to make a break into showbiz, doing radio shows and comedy clubs. His first big role was playing Windy Wales on the Bobby Benson radio show. He auditioned for and got a small role in the Broadway play No Time For Sergeants where he first met Andy Griffith. Don later reprised his role for the movie version.
Don also became a regular on the Tonight Show with Steve Allen, doing his nervous man routine for the Man-on-the-Street segments and bits in other sketches.
In 1959, the Tonight Show moved to Hollywood and Don moved with it to California. He heard that Andy Griffith was doing a new TV series about a small-town sheriff. He called Andy and suggested that the show needed a deputy. A few weeks later, Don got the part of Deputy Barney Fife. (Originally, Fife was referred to as Sheriff Andy Taylor's cousin, but the idea was later dropped.) Don won the Emmy for Best Supporting Actor five years in a row.
In 1964, Don starred in The Incredible Mr. Limpet. After that, he signed a five-year contract with Universal Pictures. He did The Ghost and Mr. Chicken (1965), The Reluctant Astronaut (1967), The Shakiest Gun in the West (1968), The Love God (1969) and How To Frame A Figg (1971).
After his movie contract was up, Don had a shortly lived variety show on NBC. He also divorced his wife, Kay, but remarried to woman named Loralee Czuchna. Don had two kids with Kay, a son and a daughter. Don started doing plays and guest appearances on other TV shows and eventually started doing movies with Tim Conway for Disney.
In 1979, Don got the role of Ralph Furley on Three's Company. After the show went off the air, Don revived his role as Barney Fife for an Andy Griffith Show reunion special. He did a few small TV appearances, including a recurring character on Matlock.
Although he hadn't had any major roles lately, Don kept himself busy with plays, doing cartoon voices and a part in Pleasentville. He eventually divorced his second wife, Loralee but was spending time with actress Francey Yarborough.