A member of Republican Proposal (PRO), Rodríguez Machado previously served as a provincial legislator of Córdoba from 1991 to 1995 for the Union of the Democratic Centre (UCEDE).

[7][8] In the 2015 general election, Rodríguez Machado ran for one of Córdoba's three seats in the Senate as the first candidate in the Cambiemos list, alongside Ernesto Félix Martínez.

[1] She was a supporter of the legalization of abortion in Argentina, voting in favour the two Voluntary Interruption of Pregnancy bill debated by the Argentine Congress in 2018 and 2020.

[11][12] On 10 December 2019, she was elected second vice president of the Senate, deputising Claudia Ledesma Abdala alongside Maurice Closs and Martín Lousteau.

[13] In the 2021 legislative election, Rodríguez Machado was the fourth candidate to the Chamber of Deputies in Córdoba in the Juntos por el Cambio list, behind Rodrigo de Loredo, Soledad Carrizo, and Héctor Baldassi.