The circuit first opened in 2008 and subsequently hosted national Argentine motorsport championships including TC2000, Top Race V6, Turismo Nacional, and Formula Renault Argentina. The 2012 rebuild transformed the facility into an internationally homologated venue capable of hosting FIM and FIA world championship events, with Zaffelli's redesign establishing the track's current 4.805 km configuration.
The circuit was intended to stage the Argentine Motorcycle Grand Prix in 2013, but a political complication intervened: the Argentine government's nationalisation of Repsol's local subsidiary, and the subsequent cancellation of gas exports from Argentina, raised safety concerns for the Honda MotoGP team given Honda's commercial relationship with the Spanish oil company. The race was postponed by one year as a result.
When MotoGP did arrive at Termas de Río Hondo in 2014, it marked the return of Grand Prix motorcycle racing to Argentina for the first time since 1999. The circuit hosted the third round of the season in both 2014 and 2015, before becoming a regular fixture on the MotoGP calendar. The Argentine Motorcycle Grand Prix has subsequently run at the circuit in 2014, 2015, 2016, 2017, 2018, 2019, 2022, 2023, and 2025.
In January 2013, the circuit also staged the first official MotoGP and Moto2 pre-season tests, giving the facility an early introduction to the world championship paddock before its race debut.
The World Touring Car Championship also used Termas de Río Hondo, with the FIA WTCC Race of Argentina held at the circuit in 2013, 2014, 2015, 2016, and 2017. In the 2013 season, Rounds 15 and 16 of the championship were run at the venue, making it the first major FIA event hosted at the rebuilt circuit.
On 6 February 2021, a fire destroyed the circuit's pit buildings. No casualties were reported. The grandstand, media centre, and pit garages were subsequently reconstructed, with the works completed in time for the 2022 Argentine Motorcycle Grand Prix to proceed as scheduled.
In March 2023, Penske Entertainment chief executive Mark Miles and vice president Michael Montri visited the circuit to assess its potential as a future IndyCar race venue, touring the facility and evaluating whether it could host a round of the NTT IndyCar Series.
Autódromo Termas de Río Hondo holds significance as the circuit that restored world-championship motorcycle racing to Argentina in the modern era. Its location in the thermal spa town of Termas de Río Hondo, far from the traditional South American motorsport centres of Buenos Aires and São Paulo, gave it a distinctive character within the MotoGP calendar. The circuit's resilience following the 2021 fire demonstrated strong institutional commitment to maintaining the Argentine Grand Prix as a permanent fixture.