In the middle of the national conflict, Santiago del Estero separated from Tucumán in 1820, coming under the control of pro-autonomy Governor Juan Felipe Ibarra.

During the 1890s, national policy makers were made aware of a little-publicized tourist route northwest of the city of Santiago del Estero, whereby, despite the abject lack of transportation or lodging amenities, a steady stream of visitors rode on horseback over craggy terrain for hours for the sake of enjoying a cluster of mineral springs rarely mentioned since Spaniards had first noticed them in 1543.

[clarification needed] Regarded as a Caudillo, by the 1990s, he was readily ordering his opponents' deaths, including those of former Governor César Iturre in 1996 and of Bishop Gerardo Sueldo in 1998.

His wife, Nina Aragonés de Juárez, was hand-picked to replace him; she was herself removed from office by the order of President Néstor Kirchner in March 2004.

Centred on the basins of the Salado and Dulce Rivers, the main crops include cotton (20% of the national production), soybean, maize and onion.

Cattle farming is also important, mainly in the east, where weather conditions make it possible, but goats, with 15% of the national production, adapt better to the rest of the province.

Important figures connected to the history of Santiago del Estero include colonel Juan Francisco Borges, leader of the Independence War (and ancestor of writer Jorge Luis Borges), as well as the revolutionary leaders Mario Roberto and Francisco René Santucho, founders of the Partido Revolucionario de los Trabajadores and the Ejército Revolucionario del Pueblo.

Among the province's most distinguished cultural figures since the 19th century have been painters Felipe Taboada, Ramon Gómez Cornet, Carlos Sánchez Gramajo, Alfredo Gogna, and Ricardo and Rafael Touriño, as well as writers Jorge Washington Ábalos, Bernardo Canal Feijóo, Clementina Rosa Quenel and Julio Carreras (h).

Amancio Jacinto Alcorta, a celebrated composer of flute concertos and religious music, also represented Santiago del Estero in Congress through much of the mid-19th century with distinction.

Renowned artists and groups include the Manseros Santiagueños, Alfredo Ábalos, Leo Dan, Jacinto Piedra and Raly Barrionuevo.

Santiago del Estero is a province known for the interference of organized crime and the high number of usurpations generated since Gerardo Zamora came to power in 2005, where peasants and landowners are threatened[19] and stripped of them.

[20] At the end of 2022, one of the many cases of victims of usurpation, where the conjunction of criminal groups and power was observed, was that of Manuel Ascencio Ardiles, who was stripped of 30 hectares of land by the President of the Superior Court of Justice.

[35] The murders, usurpations and violence that are experienced in the province are only the reflection of a well-structured drug-criminal network, with ties to the governor, the police, judges and prosecutors, this was confirmed by the consultant Douglas Farah in his report published in November of the year 2022, entitled "Case Study In Transnational Criminal Convergence: Santiago del Estero, Argentina".