The Florida congresswoman said she's running because of two words: "Never tire."
Rubio's reelection could hinge on whether Florida Republicans love Trump more than Florida Democrats hate him.
The congresswoman had been weighing whether to run for the Florida governorship or a seat in the Senate.
At a hearing on the COVID-19 Hate Crimes Act, Rep. Val Demings argued with Rep. Jim Jordan over an amendment introduced by Republicans that would prevent defunding police departments.
"Did I strike a nerve?" the Florida Democrat, who's a former police officer, shouted at her Republican colleague.
The presidency would essentially become all-powerful, Democrats said, if Congress doesn't remove Trump.