Tuberville, who also has coached at Mississippi, Texas Tech and Cincinnati, said he will seek the seat held now by Democrat Doug Jones, who defeated Republican Roy Moore in a special election on Dec. 12. Jones became the first Democrat to become a senator from Alabama since 1992.
"After more than a year of listening to Alabama's citizens, I have heard your concerns and hopes for a better tomorrow," Tuberville, 64, posted on Twitter. "I am humbled to announce the next step -- I will be a @GOP candidate for US Senate. I invite you to join my team."
The Republican primary is March 3, 2020, and the general election is Nov. 3, 2020.
U.S. Rep. Bradley Byrne, R-Mobile, also is seeking the Senate seat.
In 2017, Tuberville filed paperwork and took out a $100,000 loan for a potential campaign as governor. He ultimately decided against it, citing his support for Gov. Kay Ivey, the Montgomery Advertiser reported.
Tuberville has never run for political office before.
In coaching, he won 159 games with 99 losses over 21 years, including 85-40 in 10 seasons with Auburn as the most successful coach at the Alabama school.
He made the announcement before Auburn men's basketball team played for the first time in the NCAA Final Four -- against Virginia in Minneapolis, Minn.