Huddleston was born in Burkesville, Kentucky. After graduating from high school, he enlisted in the United States Army and served as a tank gunner in Europe during and after World War II from 1944 to 1946. He then attended the University of Kentucky, from which he graduated in 1949.

Huddleston was a manager of radio stations in Kentucky from 1949 to 1972. He entered politics in 1964 when he was elected to the Kentucky State Senate. He served as a state senator from 1965 to 1972, and served for a time as the majority leader.

In 1972, Huddleston ran for the senate seat which was being vacated by retiring Republican John Sherman Cooper. He defeated Republican Louie B. Nunn and received 51f the vote. Huddleston was reelected in 1978 with 61f the vote.

In 1984, Huddleston's Republican opponent was Jefferson County (Louisville) Judge-Executive Mitch McConnell. McConnell gained political traction with a series of television campaign ads making sport of Huddleston's attendance record in the Senate. Despite these ads, the race was very close, with McConnell only defeating Huddleston when the last returns came in (49.9Ô9.5ž It was very likely that Huddleston would have won had it not been for Ronald Reagan's gigantic landslide in that year's presidential election (Reagan carried Kentucky by over 21 points). Despite the general perception that 1984 was a disaster for Democrats, Huddleston was the only Democratic senator to lose to a Republican challenger that year.

Huddleston was known as a member of the moderate wing of the Democratic Party, as was (and continues to be) typical of party members from Kentucky.

In the late 1980s, Huddleston was the head of the English Language Political Action Committee (a.k.a. "El Pac").

After leaving the senate, Huddleston moved to Elizabethtown, Kentucky. He was married to Jean Huddleston from 1947 until her death in 2003.