As the wife of the 32nd President Juan Manuel Santos, María Clemencia served from 2010 to 2018 as the First Lady of Colombia; being the third wife of a Colombian president to serve for two periods (eight years) consecutively.

Rodriguez de Santos -or also "Tutina" as she is affectionately known-, was characterized by her glamour, sobriety and elegance; being one of the most influential fashion icons in Colombia.

The Roman Catholic ceremony took place at the Church of Our Lady of the Waters in Bogotá, and was officiated by Fr Jesús Adán Londoño Rodas.

It was attended by, among others, the then-President Belisario Betancur Cuartas and First Lady Rosa Helena Álvarez Yepes who were not only the guests of honour, but also the godparents of the couple for the ceremony.

In 1987 she married Juan Manuel Santos -then Deputy Director of El Tiempo-; this time in a civil ceremony.