[3] Domínguez received his first call-ups for the senior Ecuador national football team in May 2010 for friendlies against Mexico and South Korea.

Manager Reinaldo Rueda finally gave Domínguez his first cap on 26 March 2011 in a 2–0 friendly defeat to Colombia.

He established himself as Ecuador's first choice goalkeeper during the 2014 FIFA World Cup qualifying campaign, making 12 appearances for La Tri.

[9] On 15 June, he made his FIFA World Cup debut in a 2–1 defeat to Switzerland at the Estádio Nacional Mané Garrincha in Brasília.

Domínguez kept a clean sheet and stopped shots from the likes of Karim Benzema, Paul Pogba, and Olivier Giroud.

[16] In November 2022, Domínguez was named in Ecuador's squad for the 2022 FIFA World Cup held in Qatar.