Its first rail connection was by way of the former Andean Railway in 1870, after which the village grew rapidly with the influx of Italian and Spanish immigrants (mainly as tenant farmers).

Father Antonio Cardarelli commissioned the construction of the city's principal Roman Catholic church, the Cathedral of the Immaculate Conception, built between 1883 and 1886.

Some of the city's principal tourist draws include the Río Cuarto Racetrack, which hosts Turismo Carretera touring car racing events; and Estancia El Durazno, an estate built in 1917 belonging to former Governor Ambrosio Olmos.

[1] By its nature a multidisciplinary center in its scope a wide variety of activities, the university hosts frequent conferences, congresses, seminars, and graduate courses.

Summers are warm with frequent thunderstorms; however, the heat is often "cut" by periods of southerly winds, so that the average high is a comfortable 29 °C, despite the fact that it can reach 38 °C.

On some years, the normal winter drought extends into the spring, posing a threat to agriculture; however, at 846 mm, Rio Cuarto's climate is generally favourable for crops.