When a vacancy occurred on the United States District Court for the Western District of Missouri in 1954, Whittaker received strong backing from state and local political and bar leaders. In addition, Roy Roberts, Republican publisher of the Kansas City Star, and Arthur Eisenhower, brother of the president and a close friend of Whittaker, pushed his nomination. Thus, President Dwight Eisenhower named him a U.S. District Court judge. Two years later Whittaker was nominated to the United States Court of Appeals for the Eighth Circuit and was confirmed by the Senate on July 22, 1956.

In 1957 Justice Stanley Reed retired from the U.S. Supreme Court, and President Eisenhower nominated Judge Whittaker to take Reed's seat on March 2, 1957, apparently at the recommendation of U.S. Attorney General Herbert Brownell. Eisenhower's selection criteria and Whittaker's background were a perfect match. Like Kentuckian Reed, Whittaker was from a border state; he was a reasonable age (56); he had compiled an outstanding record as a regional corporate lawyer; he was a conservative Republican but had succeeded in being a nonpartisan attorney and jurist; and he had the all-important (to Eisenhower) experience of serving on the lower federal courts. The Senate confirmed him on March 19, 1957, without a formal roll call, making him the first justice born in Kansas and appointed from Missouri.

Justice Whittaker served only five years on the Supreme Court. Despite his previous legal and judicial experience, he found himself temperamentally unsuited for the pressured life of a U.S. Supreme Court justice. Decision-making and opinion-writing were excruciating exercises for him. Thus, during his short tenure he wrote only eight majority opinions, and none is of particular note. He voted with the majority in a number of close 5-to-4 decisions, however.

One major case in which Whittaker participated and wrote a separate opinion was Gomillion v. Lightfoot in 1960, which involved the gerrymandering of Tuskegee, Alabama. The state had redrawn the city boundaries to exclude all African American voters, making Tuskegee's city limits into a 28-sided figure. This left only four or five African American voters within the city. The affected African American voters argued that they were denied due process and equal protection under the Fourteenth Amendment and the right to vote under the Fifteenth Amendment. Whittaker wrote a concurring opinion to the unanimous decision. The majority opinion written by Justice Felix Frankfurter argued that segregating a racial minority was discriminatory and violative of the Fifteenth Amendment. Whittaker stated that this application extended the amendment to include the right to vote, as well as the right to vote in a particular district. Whittaker, however, believed that the equal protection clause of the Fourteenth Amendment was better suited to the ruling because redistricting is not a true violation of voting rights. The redrawing of the Tuskegee city limits was a clear violation of the equal protection clause of the Fourteenth Amendment.

After five years on the Court, Justice Whittaker retired, succumbing to physical exhaustion on April 1, 1962. Eventually, he went to work on the legal staff of General Motors. The ex-justice died on November 26, 1973, at the age of 72, in Kansas City, Missouri.

Because of Justice Whittaker's short and undistinguished career on the U.S. Supreme Court, no major biographies of him exist. A longer biographical entry, however, appears in Leon Friedman and Fred Israel's Justices of the United States Supreme Court, 1789-1978, vol. 4, 1980.