C.F. Pachuca
Santana first match in the Primera División de México was with C.F. Pachuca on 7 May 2000, against Toluca. He played with C.F. Pachuca for almost five years, from 2000–2005. He was transferred to Chivas de Guadalajara for the Clausura 2006 Tournament at the end of 2005. Sergio was a versatile player for Chivas, playing as a forward, striker, center attacking midfielder, and even as a defensive midfielder on occasions.