The Arizona senator won the nominating contests in Vermont, Rhode Island, Ohio and Texas, giving him the delegates needed to clinch the party's nomination with at least 1,191 delegates, CNN reported.
"I am very, very grateful and pleased to note that tonight, my friends, we have won enough delegates to claim with confidence, humility and a great sense of responsibility, that I will be the Republican nominee for president of the United States," McCain told supporters in Texas.
McCain said now the "most important part of our campaign begins," when he prepares for November's general election where he'll go head-to-head with the Democratic nominee.
Former Arkansas Gov. Mike Huckabee exited the Republican race after McCain was projected to win the four contests.
"It's now important that we turn our attention not to what could have been or what we wanted to have been, but now what must be -- and that is a united party," Huckabee said in his concession speech.