Santiago Rodríguez

Rodríguez is a youth academy graduate of Nacional. He made his official debut for the club in a 2019 Supercopa Uruguaya win against Peñarol on 4 February 2019.

Montevideo City Torque

On 3 November 2020, Montevideo City Torque confirmed they had signed Rodríguez, with the midfielder remaining at Nacional for the rest of the year.

New York City FC

On 9 June 2021, New York City FC confirmed they had signed Rodríguez on loan, with the midfielder joining the Major League Soccer side through to December 2022. He made over 50 league appearances for the club over two seasons, helping the team advance to and eventually win the MLS Cup in 2021. In September 2022, he was named the club's player of the month. Rodríguez returned to the club on a permanent contract in March 2023, ending months of uncertainty surrounding his future with the club. After returning to Torque, which had loaned Rodríguez to New York City FC, he was subject to interest from Brazilian club Bahia and stated that Major League Soccer needed to "become more important." However, Rodríguez would return to New York City FC as a Designated Player, signing a five-year deal with the club.

Botafogo

On 22 February 2026, Rodríguez signed for Brazilian club Botafogo on a fee reported to be worth up to $17 million.

Columbus Crew

On 2 September 2026, Rodríguez returned to MLS with the Columbus Crew as a Designated Player signing.

In 2019, Rodríguez represented the Uruguay under-20 team at the 2019 FIFA U-20 World Cup. In 2020, Rodríguez represented the Uruguay under-23 team at the 2020 CONMEBOL Pre-Olympic Tournament.

As of 21 October 2023

Nacional U20

U-20 Copa Libertadores: 2018 Nacional

Uruguayan Primera División: 2019, 2020 Supercopa Uruguaya: 2019 New York City

Campeones Cup: 2022 MLS Cup: 2021 Uruguay U20

South American Games silver medal: 2018