Manuela Sáenz, an Ecuadorian-born and domestic partner of Bolivian independence leader and President Simón Bolívar, is considered the inaugural First Lady of Bolivia.

Since Independence of Bolivia in 12 August 1825 to Bolívar having renounced the title on 29 December 1825.

President Lidia Gueiler Tejada, Bolivia's first female head of state, was divorced at the time of her tenure in office (1979–1980), so the position remained vacant.

[1] She had previously been married twice, first to Mareirian Pérez-Ramírez, a Paraguayan soldier and wealthy rancher, and then to a Bolivian named Edwin Möller Pacieri, but both marriages ended in divorce.

[4] Héctor Hincapié Carvajal, a Colombian politician and second husband of President Jeanine Áñez, became Bolivia's earliest First Gentleman in its history when Áñez assumed the interim presidency on November 12, 2019.