Church was an unsuccessful candidate for the Democratic nomination in the 1976 presidential election, losing to Jimmy Carter. He is known for heading the Church Committee, which investigated abuses in the U.S. intelligence agencies.

Frank Church was raised in Boise, Idaho. In his youth, Church admired William E. Borah, who then represented Idaho in the United States Senate. Church graduated from Boise High School in 1942, where he served as student body president. As a junior in 1941, he won the American Legion National Oratorical Contest. The prize was sufficient to provide for four years at the college of the winner's choice. Church chose Stanford University, enrolling in 1942.

In 1943, Church enlisted in the U.S. Army and served as a military intelligence officer in the China-Burma-India theater. Following his discharge in 1946, he returned to Stanford to complete his education, receiving his bachelor's degree in 1947.

Also in 1947, he married Bethine Clark, daughter of Chase A. Clark, a former Democratic governor of Idaho, and entered Harvard Law School. After one year at Harvard, Church transferred to Stanford Law School, when he thought the cold Massachusetts winter was the cause of a pain in his lower back. The pain did not go away and the problem was soon diagnosed as testicular cancer. After one of his testicles and glands in his lower abdomen were removed, Church was given only a few months to live. However, he rebounded from the illness after another doctor started X-ray treatments. This second chance led him to later reflect that "life itself is such a chancy proposition that the only way to live is by taking great chances." In 1950, Church graduated from Stanford Law School and returned to Boise to practice law.

Frank and Bethine had two sons, Frank Forrester Church IV, who died in 2009, and Chase Clark Church, who lives in Boise.

Church became an active Democrat in Idaho and after an unsuccessful try for the State Legislature in 1952, he ran for the United States Senate in 1956. After a closely contested primary election against former Senator Glen H. Taylor, Church handily defeated Republican incumbent Herman Welker in the general election. At the age of 32, Church became the fifth youngest member ever to sit in the U.S. Senate. Church was reelected three times (1962, 1968 and 1974), the only Democrat ever to win reelection to the U.S. Senate from Idaho.

Upon entering the Senate in January 1957, Church made the mistake of voting on a measure against the wishes of Democratic Majority Leader, Lyndon Johnson, and Johnson punished Church by all but ignoring him for the next six months. Church found solace from Republican Minority Leader, William Knowland. However, Church managed to find his way into Johnson's good graces by providing key assistance in getting the Civil Rights Act of 1957 passed. LBJ was so grateful he made the young Idahoan a veritable protégé, rewarding him with plum assignments, such as a seat on the prestigious Senate Foreign Relations Committee, a position which allowed Church to follow in the footsteps of his idol, William Borah. Recently declassified documents show that the young veteran also challenged his mentor, behind closed doors, after the 1964 incident in the Gulf of Tonkin , making this prescient warning: “In a democracy you cannot expect the people, whose sons are being killed and who will be killed, to exercise their judgment if the truth is concealed from them."

In 1967, a recall campaign was waged against Church by Ron Rankin, a Republican county commissioner in Kootenai County in northern Idaho. Rankin unsuccessfully sued Idaho's secretary of state to accept recall petitions. The U.S. District Court for Idaho ruled that the state's recall laws did not apply to U.S. senators and that such a recall would violate the U.S. Constitution. Allan Shepard, Idaho's attorney general at the time, agreed with the court's decision.

"It must be pointed out that a United States senator is not a state officer but a federal officer whose position is created by Article I, Section I of the United States Constitution," Shepard wrote in a June 17, 1967, opinion for the secretary of state. "There seems to be no provision for canvassing the votes of a recall election of a United States senator." Most commentators at the time believed that the recall attempt strengthened Church politically by allowing him to play the role of political martyr and he was reelected in the next year's election over Republican Congressman George V. Hansen 60% to 40%.

Church was a key figure in American foreign policy during the 1970s, and served as chairman of the Senate Committee on Foreign Relations from 1979 to 1981. Following the instinct that led him to ask questions early on (see above), Church was one of the first senators to publicly oppose the Vietnam War in the 1960s, although he had supported the conflict earlier. He was the co-author of two legislative efforts to curtail the war: the Cooper-Church Amendment of 1970, and the Case-Church Amendment of 1973.