In 2000, Mejía ran for president as the candidate of the left leaning Dominican Revolutionary Party (PRD) on a program to increase health, education, and social security services through tax hikes. He led the field in the 2000 presidential election, taking 49.87 percent of the vote in the first round. His main opponents, Danilo Medina and former president Joaquín Balaguer, received 24.9% and 24.6% of the vote, respectively.
Mejía's first presidential campaign in 2000 won him the first Dominican presidency under then new electoral rules that required a "50 más 1" (50 percent plus one of the total votes in order to win in the first voting round.) This was in stark contrast to the late PRD leader, José Francisco Peña Gómez, who unsuccessfully ran for office three times consecutively (1990, 1994 and 1996) and never received the support that Mejia received in his first attempt.
While holding the seat of Head of State, Mejía actively sought to change the then current constitution in order for it to allow consecutive presidential re-elections. This was achieved with the aid of his party's majority stake at both legislative chambers (Senate and Lower Chamber). The original constitution prevented the previous president from contending against him in 2000.