In 1979, Espino received his degree as an electrical technician from the Regional Technological Institute of Durango; a year before, he had joined the PAN.

He was a frequent representative of the party in electoral matters, as well as a Scout and an instructor teaching business training courses in Ciudad Juárez and Durango; additionally, between 1978 and 1985, he was a middle and high school teacher at various educational institutions in Durango and Ciudad Juárez, as well as an administrator of an accounting and administration company.

[1] 1984 also saw Espino get involved in the founding of the Center of Hispanic-American Studies in El Paso, Texas,[1] while the next year, he began a three-year term as president of the Mexican Scouts Association.

[1] Also during this time, he was a founding member and vice president of the Foundation for the Cultural Diffusion of America's Half Millennium, between 1989 and 1992.

[1] In 2005, Manuel Espino succeeded Luis Felipe Bravo and became the 18th president of the National Action Party, a position he held for two years.

[1][3] However, during this time, a rift began to grow between Espino and the PAN president, Felipe Calderón Hinojosa; he also disagreed with the federal government's security strategy, calling it "one of the bloodiest".

He is a secretary on the National Defense and Public Security Committees and also holds a seat on the Commission for the Strengthening of Federalism.

[20] Espino has written various books, including Señal de Alerta (2008), which warned that Manlio Fabio Beltrones might run for president in 2012;[21] Volver a Empezar (Start Over, 2010); La guerra injusta de Ciudad Juárez (The Unjust War of Ciudad Juárez, 2010), in which he called the drug war started by Calderón "the bloodiest conflict on Mexican soil since the Revolution";[22] El Poder del Águila (The Power of the Eagle, 2012); and Mexicanos al Grito de Paz (2015).