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They started in 1969, when entrepreneurs from San Luis Potosí decided to create a professional basketball team, not just to participate in the Circuito Mexicano de Básquetbol (CIMEBA), to become one of the best teams in the country.

Their beginning was rather shaky, but shortly thereafter they found a winning strategy and gameplay, which was then seen in their results. The Santos were always among the best teams in CIMEBA, and in the 1971-1972 season they achieved their first national championship.

The second national championship came in 1980 and, after the season finished, three players were selected to be part of the national team. The third championship was obtained in the 1997-1998 season.

The team's most important achievement was in the 2004 season, now playing in the Liga Nacional de Baloncesto Profesional (LNBP), when they were crowned after winning against the Halcones UV Xalapa and took the trophy back to San Luis Potosí.

Another memorable match was away from home court in 2004, between Los Santos Reales and Fuerza Regia de Monterrey, the latter having Dennis Rodman in their team. The Santos Reales won the match with a score 95-84.

At 2009, due to economic issues, the team was forced to leave every professional sport competition.

At 2015, with a new administration and more financial support, the team returned to the LNBP to play the 2015-2016 season, but under the new name of C.B. Santos San Luis.

At 2020, due to the absence of people at the stadium, consequence of the COVID-19 pandemic, the team decided not to participate in the 2020 LNBP season, hoping to return for the next one.

In July 2023, the return to the LNBP was announced, now under the name of Santos del Potosí.