Vázquez Mota began her political career with PAN with the Asociación Coordinadora Ciudadana and a member of the Secretaría de la Mujer. In 1996, she was asked to return to Mexico City to become a representative in Mexico’s federal legislature (Cámara de Diputados), because of her economics expertise. At this time, she met the then president of PAN, Felipe Calderón . She was elected to the 2000-2003 federal legislature (Cámara de Diputados), leading the sub-coordination of Economic Policy. She was then appointed as the first female secretary of Desarrollo Social (Social Development) known by its Spanish acronym of SEDESOL. While discrete, it was known that she did not get along with then First Lady Martha Sahagún . She remained in that position until 2006, when she resigned to work for the Calderón campaign.