"My priorities have always been my faith, my family and my country. And at this stage in my life, and after nearly 12 years of public service in Florida and Washington, it's time I return to Florida and my family," Martinez wrote in an e-mail to friends and supporters.
He earlier had announced plans to retire in 2010.
Martinez's resignation means that Crist, the leading Republican candidate to succeed Martinez, will name someone to serve the remainder of the term. Martinez told reporters during a news conference at Orlando International Airport that he was "absolutely not" pressured to resign and that he trusted the governor to make the right decision in replacing him.
Crist, who holds a big lead in the polls, told reporters Friday that he would not appoint himself. Instead, he said, he would look for someone to keep the seat warm until the November 2010 election.
In brief remarks after a tour of MacDill Air Force Base in Tampa, Crist said: "We will undertake a very thorough, very comprehensive, thoughtful process" to fill Martinez's seat.
Earlier in the day, Senate Majority Leader Harry Reid (D-Nev.) said that he would remember Martinez as a gentleman, and he praised the Floridian's work on travel promotion legislation and immigration.
According to advisors to Martinez and Crist, candidates on the short list to fill out the Senate term include former Florida Secretary of State Jim Smith; former state House Speaker Allan G. Bense; former Sen. Connie Mack, Crist's political mentor; and former Gov. Bob Martinez, who served from 1987 to 1991.
Sen. Martinez's storybook journey into politics began in 1962, when he was one of 14,000 children brought out of Cuba in the Roman Catholic humanitarian effort called Operation Peter Pan. He went to law school, practiced in Orlando for 25 years, and eventually won election as Orange County chairman. President George W. Bush appointed him secretary of Housing and Urban Development in 2001, a post he would leave to run for the Senate.
But Martinez's stay in the chamber was rocky from the beginning. In his 2004 GOP primary against Bill McCollum, his staff put out a memo attacking McCollum for being a "darling of homosexual extremists" for supporting hate-crime laws.
Martinez would later distance himself from the attack and blame a staffer.