Graham, a senator from South Carolina, made the announcement in a Youtube video message, which said he was suspending his campaign for president, Xinhua reported.
The move was expected because his campaign never took off, and he has been stuck in low single digits in national polls.
As of Monday, Graham gained only 0.5 percent of support in the RealPolitics' average of recent national polling. Even in his home state of South Carolina, his support fell to 1 percent.
Graham's poor poll numbers disqualified him from taking part in the previous five major Republican presidential debates.
The senator, a member of the Senate Armed Services Committee, had hoped that his experience on national security could help his campaign at a time when security is one of the top concerns for Americans.
Graham is the fourth Republican candidate to quit the presidential race following former Texas governor Rick Perry, Wisconsin Governor Scott Walker and Louisiana Governor Bobby Jindal.