Clyde MacDonald Jr. was born in 1929 in Old Orchard Beach to Nellie MacDonald and Clyde MacDonald Sr., who were both of Canadian descent. The oldest of four children, MacDonald enlisted in the Army and served during the Korean War in Germany. After he left the military, he became interested in politics at the local level. He attended Portland Junior College for two years and then Bates for two years. He later earned a doctorate at the University of Maine while teaching undergraduate classes there. Meanwhile, he was becoming active in local Democratic politics. As he became more involved with politics, MacDonald found himself in more regular contact with Senator Muskie. Despite occasional policy disagreements, notably about the Vietnam War, which MacDonald opposed, MacDonald eventually went to work with Muskie, becoming an aide and close personal adviser.
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L'Hommedieu, Andrea, "MacDonald, Clyde, Jr. oral history interview" (1999). Edmund S. Muskie Oral History Collection. 227.