In 1964, Walker was a delegate to the Republican National Convention, which met in San Francisco, California, and he ran as a Republican in, in the central eastern part of the state. He unseated 11-term incumbent W. Arthur Winstead by some 7000 votes, an 11% margin, the first Republican breakthrough in Mississippi since Elza Jeffords served a term in Congress from 1883 to 1885. Walker's victory is considered to have been strongly influenced by the campaign of Barry Goldwater, who carried Mississippi in the 1964 presidential election with 87% of the vote. Goldwater won many of the counties in the district with greater than 90% of the vote; two, Holmes and Noxubee counties, gave him a staggering 96.6%, tied for his best showing in the nation. After winning the election, Walker's first public appearance was to speak at a meeting organized by the group Americans for the Preservation of the White Race. At a Republican fundraiser at the Mississippi Coliseum in the capital city ofJackson on June 20, 1983, US President Ronald Reagan would tell the following anecdote:
Former Congressman Prentiss Walker, who I understand is here today, tells a story about his first campaign. He dropped in on a farm and introduced himself as a Republican candidate. And as he tells it, the farmer's eyes lit up, and then he said, "Wait till I get my wife. We've never seen a Republican before."
And a few minutes later he was back with his wife, and they asked Prentiss if he wouldn't give them a speech. Well, he looked around for kind of a podium, something to stand on, and then the only thing available was a pile of that stuff that the late Mrs. Truman said it had taken her thirty-five years to get Harry to call "fertilizer."
So, he stepped up on that and made his speech. And apparently he won them over. And they told him it was the first time they'd ever heard a Republican. And he says, "That's okay. That's the first time I've ever given a speech from a Democratic platform."
Walker relinquished his House seat after only one term. He instead challenged U.S. Senator James Eastland. He ran well to Eastland's right and accused the veteran senator of being too friendly with US President Lyndon Johnson and of not doing enough to block integration-friendly judges in his position as chairman of the Senate Judiciary Committee. Like Eastland, Walker had voted against the Voting Rights Act of 1965 and focused only on the white vote in his Senate race. In the words of Claude Ramsey, president of the Mississippi AFL-CIO, Walker tried to "outsegregate" Eastland, but most white voters stayed with Eastland, who finished with 65.6% of the vote. With 105,652 votes, Walker polled 26.7% at the general election. His supporters included blacks in southwestern Mississippi, which came as a surprise because of Walker's open support for segregation. Black voters had entered the political process under the Voting Rights Act of 1965 and carried Claiborne and Jefferson Counties for Walker in protest of Eastland as a "Democratic Regular." Years later, Wirt Yerger, the chairman of the Mississippi Republican Party in the 1960s, said that Walker's decision to relinquish his House seat after one term for the vagaries of a Senate race against Eastland was "very devastating" to the growth of the Republican Party in Mississippi. In 1966, Mississippi House RepresentativeLewis McAllister of Meridian, the first Republican elected to the Mississippi House of Representatives since Reconstruction, sought to hold Walker's House seat for the Republican, but victory went to fellow State Representative Gillespie V. "Sonny" Montgomery, also of Meridian, who held the seat for 30 years. Walker tried to unseat Montgomery in 1968 but got only 30% of the votes. When Walker again ran for the Senate against Eastland in 1972, as an Independent, rather than a Republican, he drew only 14,662 votes. The Moderate RepublicanGil Carmichael, a former critic of Walker, trailed with 249,779 votes, as Eastland won handily, 375,102.
Private life
Walker and his wife, the former Dimple Howell, the last surviving of six children of the former Emily Dorilla Johnson and John Fleming Howell, had two daughters, Treta Walker Butler and husband James of Mize and Jan Walker Magee of Magee, Mississippi. Prentiss and Dimple Walker are interred in Mize at Zion Hill Missionary Baptist Church Cemetery.