Crist said he would make the run official Monday during a rally in St. Petersburg, Fla. He filed the necessary paperwork on Friday.
His announcement has been widely expected and early polling has shown him leading in a matchup against Republican Gov. Rick Scott, whose approval rating has foundered.
Crist decided to forgo a campaign for a second term as governor in 2010 in order to seek the open Senate seat at the time. Crist ran as an independent after polls showed him trailing badly in the GOP primary against Marco Rubio, who eventually won the seat.
Crist has since become a Democrat, backing President Obama in 2012. He registered as a Democrat last December, tweeting a picture of himself with his registration form at the White House.
Scott will be out of the country for Crist’s announcement but Scott’s political action committee will begin running $500,000 worth of ads attacking Crist on Monday, according to The Tampa Bay Times.