Vazquez Mota was elected late Sunday with 55 percent of votes from National Action Party (PAN) members, with 86.7 percent of votes counted, meaning she had a large enough lead to avoid a second round run-off.
Former finance minister Ernesto Cordero scored 38.1 percent and Santiago Creel, an ex-interior minister, had 5.21 percent.
The president of the PAN electoral commission said the results showed an "irreversible" tendency.
"I'm going to be the country's first female president," Vazquez Mota said late Sunday.
She is the first female to stand for president from one of the three main parties.
The former lawmaker and ex-minister of both education and social development is seeking to take over from President Felipe Calderon, who can only serve one six-year term under the constitution.
Calderon's failure to stem raging drug violence has hurt support for his PAN party and many predict a return of the Institutional Revolutionary Party (PRI), which ruled Mexico for more than seven decades to 2000.
According to opinion polls, the current favorite is PRI candidate Enrique Pena Nieto, the former governor of central Mexico state.
Mexico City's former mayor Andres Manuel Lopez Obrador -- who fought a long, unsuccessful campaign to show he won the tight 2006 presidential election -- is again standing for the leftist Party of the Democratic Revolution (PRD).