Born in Humboldt, South Dakota, Pressler is a graduate of the University of South Dakota, Oxford University (as a Rhodes Scholar), and Harvard Law School. He became a lawyer, and then served in the Vietnam War in the United States Army from 1966 until 1968. After serving for several years under South Dakota's Secretary of State, he was elected to the House of Representatives from 1975 to 1979. He was a Senator from South Dakota from 1979 to 1997, and was chairman of the Committee on Commerce, Science and Transportation.

Pressler is noted for being the only Member of Congress to refuse to take a bribe from undercover FBI agents during the Abscam investigations in 1980.

In 1996, Tim Johnson defeated Pressler, who was running for a fourth term in the senate. Pressler was the only incumbent Republican senator to lose reelection that year. After his reelection defeat, Pressler passed the New York bar and worked as a lawyer there, serving on several corporate boards and as a teacher at the University of California, Los Angeles.

Pressler attempted a political comeback in 2002 by running for the open at-large House seat he once held. However, he was defeated in the Republican primary by popular Gov. Bill Janklow, who went on to defeat Democrat Stephanie Herseth in the general election. Pressler was since appointed as an official observer to the Ukraine national election in December 2004.