On August 18, 1918, incumbent senator Ollie M. James died.
Stanley appointed George B. Martin to finish James' term, which was to expire on March 3 of the following year.
James had already been nominated for re-election in 1918 by the Democratic primary, and the task of selecting the party's new nominee fell to the Democratic State Committee, which nominated Stanley.
Stanley enjoyed the advantage of a united Democratic party; J. C. W. Beckham supported Stanley for this seat so Stanley would not challenge him for his own seat when he faced re-election.
The Republicans chose a relative unknown, Dr. Ben L. Bruner.
Stanley was attacked for his veto of the German language bill and for his long-standing views against temperance.
Though the national mood was against the Democrats, a letter of support from President Woodrow Wilson bolstered Stanley's campaign, and he defeated Bruner by more than 5,000 votes.
He resigned as governor to assume the Senate seat in May 1919.
As a Democrat in a mostly Republican Senate, he wielded little influence.

When Stanley sought re-election to his seat in 1924, he faced an uphill battle.
No Kentucky senator had been re-elected to his seat in over forty years (though senators had been popularly elected only since 1914).
His opposition to prohibition cost him the support of pro-temperance voters and Democratic governor William J. Fields.
He was also opposed by the Ku Klux Klan, then a powerful organization in the state, because of his opposition to bigotry and secret organizations.
His Republican opponent Frederic M. Sackett secured the support of the Beckham wing of the Democratic Party.
Despite having his own private stock of liquor, Sackett took a pro-temperance position in the campaign and was endorsed by the Anti-Saloon League.
Louisville Courier-Journal editor Robert Worth Bingham added his endorsement, calling Sackett "one of the best men I know".
In the general election, Stanley lost his seat by almost 25,000 votes.
Sackett's victory meant Kentucky would have two Republican senators for the first time in its history.
On August 18, 1918, incumbent senator Ollie M. James died. Stanley appointed George B. Martin to finish James' term, which was to expire on March 3 of the following year. James had already been nominated for re-election in 1918 by the Democratic primary, and the task of selecting the party's new nominee fell to the Democratic State Committee, which nominated Stanley. Stanley enjoyed the advantage of a united Democratic party; J. C. W. Beckham supported Stanley for this seat so Stanley would not challenge him for his own seat when he faced re-election. The Republicans chose a relative unknown, Dr. Ben L. Bruner. Stanley was attacked for his veto of the German language bill and for his long-standing views against temperance. Though the national mood was against the Democrats, a letter of support from President Woodrow Wilson bolstered Stanley's campaign, and he defeated Bruner by more than 5,000 votes. He resigned as governor to assume the Senate seat in May 1919. As a Democrat in a mostly Republican Senate, he wielded little influence.
When Stanley sought re-election to his seat in 1924, he faced an uphill battle. No Kentucky senator had been re-elected to his seat in over forty years (though senators had been popularly elected only since 1914). His opposition to prohibition cost him the support of pro-temperance voters and Democratic governor William J. Fields. He was also opposed by the Ku Klux Klan, then a powerful organization in the state, because of his opposition to bigotry and secret organizations. His Republican opponent Frederic M. Sackett secured the support of the Beckham wing of the Democratic Party. Despite having his own private stock of liquor, Sackett took a pro-temperance position in the campaign and was endorsed by the Anti-Saloon League. Louisville Courier-Journal editor Robert Worth Bingham added his endorsement, calling Sackett "one of the best men I know". In the general election, Stanley lost his seat by almost 25,000 votes. Sackett's victory meant Kentucky would have two Republican senators for the first time in its history.
Augustus Owsley Stanley