The endorsement letter, obtained by The Associated Press on Tuesday, marks a split between the two Republican senators representing South Carolina, which holds the first southern presidential primary.
"I'm writing to ask for your support of Governor Mitt Romney for President," DeMint says in the four-page letter. "We must elect a President in 2008 who is up to the task, and I need you to encourage Mitt to run."
DeMint's split is seen by some as a move to find a conservative alternative to McCain, but it's not that much of a surprise.
DeMint, who was elected in 2004, held a fundraiser for Romney last year. His support will "shake some money out," but endorsements don't win elections, Clemson University political scientist Dave Woodard said.
McCain and Romney have both set up exploratory committees and started raising money for presidential bids but haven't formally declared they're running.
DeMint, chairman of the Senate's conservative GOP Steering Committee, said he wrote the letter after talking or meeting with most of the likely 2008 GOP candidates.
"I have not seen people respond to a candidate with the enthusiasm — with the real energy — that I saw them respond to Romney," DeMint said in a telephone interview. "It was pretty much Reagan-like."
DeMint said he remains McCain's friend, noting he co-sponsored a bill with him last week. The same is true for Graham. They work together on most issues, but disagree on some, DeMint said.
DeMint's choice may also be at odds with South Carolina Gov. Mark Sanford, who supported McCain in 2000 in a bitter loss to President Bush after the senator won in New Hampshire. Sanford hasn't yet endorsed a candidate.
DeMint is "splitting not just from Graham, but from Sanford and perhaps leading some of the Bush faction that doesn't want to go over to McCain," said Larry Sabato, director of the University of Virginia Center for Politics. McCain "is not conservative enough for many of the conservative Republicans of South Carolina."
DeMint said the letter is being sent to several thousand supporters, and is being paid for by his PAC and Romney's exploratory committee.
"Some of the Bush people from 2000 don't want to support McCain no matter what," Sabato said.