MacGregor was born in Minneapolis, Minnesota, and graduated cum laude from Dartmouth College in 1944 and the University of Minnesota Law School in 1946. He was elected to the U.S. House of Representatives in 1960, defeating six-term Democratic incumbent Roy Wier, and served in the 87th, 88th, 89th, 90th, and 91st congresses, January 3, 1961 – January 3, 1971.
In 1963, MacGregor appeared in a satirical revue by Dudley Riggs' Brave New Workshop. He was a delegate to the 1964 and 1968 Republican National Convention from Minnesota. He was an unsuccessful candidate for U.S. Senator from Minnesota in 1970, running against former Democratic Vice President Hubert Humphrey. MacGregor was Assistant to Richard Nixon for congressional relations in 1970, Counsel to the President on congressional relations (1971–1972), Chairman of the Committee to Re-elect the President (July to November 1972) following John Mitchell's resignation from the position in the Watergate political scandal.
After 1973, he left politics. He continued to live in Washington, D.C., worked for United Technologies Corporation, and was on the boards of the National Symphony Orchestra and the Wolf Trap Foundation.
- Moses, George (1963-07-23). "Congressman's Barbs Make a Hit". Eugene Register-Guard. p. 8. Retrieved 2011-01-12.
- Saxon, Wolfgang (2003-02-14). "Clark MacGregor, 80, Leader Of Nixon Campaign in 1972". New York Times. Retrieved 2011-02-12.