During the Second World War he interrupted his schooling to serve as a pilot in the air transport service of the United States Navy, flying DC3's across country (1943–1946), and was discharged as a lieutenant.

On January 31, 1962, Anderson appointed Pearson to the United States Senate to fill the vacancy caused by the death of Andrew F. Schoeppel.

Following the Kent State shooting in 1970, Pearson shifted his position to oppose the bombing of Laos and Cambodia during the Vietnam War.

When a group of senators led by Walter Mondale of Minnesota set out to change the filibuster rule, which had been used to block civil rights legislation, they asked Pearson to join them.

Those successes included the creation of the airport/airways trust fund, which allowed for the expansion of the nation's airports and air traffic system, and the deregulation of "new" natural gas, which brought increased production of that clean-burning fuel.

With Democrat Phil Hart of Michigan, Pearson sponsored the first major campaign reform legislation following World War II.

Pearson was a member of the Wednesday Club, a group of moderate and liberal Republican senators who met for lunch to discuss issues.

He dealt with this criticism by providing strong constituent service and championing Kansas interests, especially the aviation, oil and gas, and cattle industries.

[6] After leaving the Senate Pearson had a relationship with the Washington, D. C. office of the law firm of LeBoeuf, Lamb, Lieby and MacRae.

A fellowship program named for Pearson allows foreign service officers to work temporarily in other branches of government, including state and local, to learn more about domestic politics.