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James Edward Murray was born in St. Thomas, Ontario, on May 3, 1876, the son of Irish immigrants. He was named after a wealthy uncle from Butte, Montana, who later financed his education at New York University Law School. He became an American citizen in New York. Upon his uncle's urging, Murray moved to Butte after graduation in 1901 to establish his legal practice. It was in Butte that Murray met and married Viola Edna Horgan, with whom he had six sons.

Murray became active in Democratic Party politics in Butte, and earned the party votes by working for a time alongside the miners in the copper industry. After inheriting a sizable portion of his uncle's fortune, Murray spent most of the 1920s pursuing business interests. His considerable loss in the stock market crash of 1929 left Murray with an embittered view of eastern financiers, an attitude he would carry through his years in politics.

In 1931, Murray, the Democratic Party Chairman of Silver Bow County, became an early convert to the presidential camp of Franklin D. Roosevelt. As a result of his work on the candidate's behalf, he earned an appointment as a member of Montana's Public Works Administration Advisory Board. It was through that appointment that Murray gained first hand knowledge of Montana's drought-stricken farmers, who he would take an active interest in throughout his political career.

In 1934, Murray, with the support of a number of prominent Butte politicians, decided to seek election to the final two years remaining in the Senate term of the late Thomas J. Walsh. Murray won the election with labor support in Butte, and, riding on the political coat tails of Roosevelt and senior Montana Senator Burton K. Wheeler, Murray, at 59, began his senate career. He was an avid supporter of Roosevelt's domestic program, a loyal party man, and an isolationist in the area of foreign affairs.

Wheeler and Murray started out as political allies, but the relationship soon turned sour. One deciding factor that split their union was their differences over the president's Supreme Court packing plan. Wheeler was against it. The other main factor causing the split was Murray's transition from an anti-British isolationist to an outspoken proponent of Roosevelt's foreign policy leading to World War II. At that time, Wheeler was still an avid proponent of isolationism. The feud came to a peak during Murray's 1942 re-election bid, when Wheeler openly tried to undercut Murray's bid in the Democratic primary. The two senators attacked each other on statewide radio. Murray won the election by an extremely narrow margin, and returned to Washington, D.C.

During the war Murray became an avid supporter of small business, and Murray's resolution created the Senate's Special Committee on Small Business, with him as the committee's first chairman. He used his influence in the committee to introduce bills designed to assist America's small businesses, securing for them highly sought after military contracts. At the close of the war, Murray's prime concern was the loss of those wartime contracts, and he drafted reconversion legislation to ease the burden on the small businesses. These legislative bills and Murray enjoyed the support of the Senate Republicans, because of America's free enterprise system.

During the Truman and Eisenhower administrations, Murray did not fare so well with the Republicans or the conservative Southern Democrats; the conservative coalition managed to thwart or alter virtually all of Murray's legislation. An example of this was the Murray sponsored bill, the Employment Act of 1946. The bill was to establish a formal system of compensatory government spending to ease the burden of the cyclical dips in the private economy, but the law that emerged from the Senate virtually eliminated that principle.

Another obstacle to Murray's political goals during the 1940s was the medical lobby who were fighting Murray's legislation to provide a nationwide system of health insurance. Physicians and drug companies, led by the American Medical Association, managed to block all of the various Murray measures that they collectively labeled "socialized medicine." Despite these opponents, other Murray sponsored bills eventually became law, such as the "Wagner-Murray-Dingell" bills which extended Social Security coverage, allowed for federal dollars for hospital construction, and provided Medicare for senior citizens.

Presidential opposition also hampered Murray's aspirations. Harry Truman and the Montana senator parted company when Truman would not support Murray's plan for the Missouri River basin. Murray wanted to throw his support behind a plan to unify Missouri basin development under jurisdiction of a single regional authority after a series of catastrophic floods. Truman allied himself with the downstream advocates of navigation and flood control, and Murray's plan lost out to Truman and the southern senators who chaired key committees and thwarted his MVA legislation.

Murray, in turn, tried to use his influence as the chairman of the Senate Labor Committee to block a number of bills designed to alter the pro-union bend of Wagner's National Labor Relations Act. In the end, he could not prevent the Republican 80th Congress from passing the Taft-Hartley Act.

Murray's unfaltering devotion to the labor workers did not go unnoticed in Montana. Murray, with the support of the miners from Butte, timber workers, the railroad brotherhoods, and scores of lesser unions, was able to defeat powerful Republican opponents in a series of narrow election victories. In the most bitter of those elections, Murray faced a powerful opponent in the state's eastern district congressman, Wesley A. D'Ewart, in 1954. Murray's advanced age became an issue. D'Ewart also accused Murray of being used as a tool of the international Communist conspiracy. The basis for these attacks came with Murray's strong advocacy of a close American-Soviet friendship during the war, along with the senator's votes against many of the post-war Communist-curbing bills. Murray still won the election.

The senator used his influence as the Senate's Interior Committee Chairman to secure western water projects that led to congressional approval and funding for large dams in Montana at Canyon Ferry on the Missouri River, Yellowtail on the Bighorn, Hungry Horse on the Flathead, and Libby on the Kootenai. With these dams, Murray was an early convert to the causes of energy conservation and environmental protection. Even in an era in which these issues were not yet popular, Murray supported numerous bills that called for environmental protection, a national system of wilderness areas, development of wind energy, and curbing air pollution.

Murray gained national attention when he sponsored bills providing for the admission of Alaska and Hawaii to the union. He also gained attention when he, along with Montana Congressman Lee Metcalf, pushed for an ambitious program designed to provide massive federal aid for public schools. The Murray-Metcalf Bill was direct precursor of the Elementary and Secondary Education Act that became law several years following Murray's death.

In 1960, Murray's declining health forced him into retirement. He died four months after leaving the Senate on March 23, 1961.