McClure attended public schools in Payette and joined the U.S. Navy at age 18 during World War II, and served from 1942 to 1946. McClure graduated from the Navy Program at the University of Idaho-Southern Branch (now Idaho State University) in Pocatello in 1943. After his discharge from the Navy, he entered the College of Law at the University of Idaho in Moscow, and graduated in 1950. He is an esteemed member of the Delta Omicron Chapter of Sigma Nu Fraternity.
From 1950 to 1956, he served as prosecuting attorney for Payette County; he also served as city attorney for Payette from 1953 to 1966. During this span, he was also a member of the Idaho State Senate, serving from 1961 to 1966.
In the 1966 election, McClure ran for the U.S. House from Idaho's first Congressional district. He won the race, defeating incumbent Compton I. White, Jr., and was reelected in 1968 and 1970.
McClure ran for the open U.S. Senate seat (Class II) in 1972, vacated by the retirement of Len Jordan. In the general election he defeated the Democratic nominee, William E. "Bud" Davis, the president of Idaho State University. McClure was reelected by wide margins in 1978 and 1984. The seat was occupied by William Borah for over three decades (1907–1940), and has been continuously held by Republicans since 1949, over 67 years.
In 1981, McClure joined Republican colleagues Jesse Helms of North Carolina and fellow Idaho senator Steve Symms in an unsuccessful fight to return to a purchase requirement for participation in the food stamp program. Helms cited a Congressional Budget Office study which showed that 75 percent of the increase in food stamp usage had occurred since the purchase requirement was dropped in 1977. Senators voted 33 to 66 against the Helms-McClure position. "It's obvious the majority of the Senate is not really concerned about constraining the growth of the food-stamp program," McClure said.
In 1984 McClure ran for Senate Majority Leader, but was defeated by Senator Bob Dole of Kansas, who three years earlier had led the intraparty opposition to the Helms-McClure position on reinstating the purchase requirement for food stamps.
During his 18 years in the Senate, McClure served as the chairman of the Committee on Energy and Natural Resources from 1981 to 1987. In this capacity McClure emerged as an early proponent of electric cars and energy independence. He also chaired of the Senate Republican Conference from 1981 to 1985.
At age 65, McClure declined to run for a fourth term in 1990. Republican congressman Larry Craig of Midvale easily won McClure's Senate seat in November 1990 and served three terms, succeeded by Jim Risch.
After leaving the Senate, McClure became a mining consultant and lobbyist in Washington, D.C., founding the firm of McClure, Gerard, & Neuenschwander. Up until his death McClure maintained a residence in McCall.
In October 1995, the new home of the College of Mines and Earth Resources at the University of Idaho was dedicated as James A. McClure Hall. On December 12, 2001, the Federal Building and U.S. Courthouse in Boise was renamed for McClure.
In December 2008, the 83-year-old McClure suffered a stroke and was sent to the intensive care unit at Saint Alphonsus Regional Medical Center in Boise. Although initially he was expected to recover, McClure died at the age of 86 on February 26, 2011.Idaho Public Television – McClure and biographer on Dialogue in December 2007