A conservative Republican, Paul Fannin was elected Governor of Arizona in 1958, defeating Attorney General Robert Morrison by nearly 30,000 votes. He was sworn into office on January 5, 1959. He was re-elected in 1960 and again in 1962. During his tenure, Fannin increased funding for the public school system by raising sales taxes, equalized property taxes, established the first medical school in the state, and created the Arizona-Mexico Commission to promote tourism and trade across the border. He also served as chairman of the Western Governors Association, as well as a member of the Executive Committee of Council of State Governors and of the National Civil Defense Advisory Council. In 1964, when Senator Barry Goldwater declined to seek re-election in order to run for President of the United States, Fannin was elected to succeed him in the U.S. Senate. He narrowly defeated Democrat Roy Elson, an aide to Senator Carl Hayden, by a 51%-49% margin. He was re-elected to a second term in 1970, receiving 56% of the vote.[6] He did not seek re-election to a third term in 1976.

During his Senate career, Paul Fannin was a hard-line conservative, often voting with Senator Goldwater on the issues, including his vote against the Equal Rights Amendment in 1972. As the ranking Republican on the Senate Interior Committee, he was a spokesman for Presidents Richard Nixon and Gerald Ford on energy policy; he opposed new limits on strip mining and tighter reins on federal lands. He also joined conservative Democratic Senators to preserve the clause of the Taft–Hartley Act that let the states decide whether to prohibit mandatory membership for workers in unionized shops. In 1968, he became the principal sponsor behind the Central Arizona Project, which diverted water of the Colorado River to central and southern Arizona. During part of his tenure in the Senate, Paul Fannin sat at the candy desk. He continued to live in Phoenix, Arizona, until he died of a stroke on January 13, 2002. He is buried at Greenwood Memory Lawn Cemetery in Phoenix.