Founded in 1983 as Club Santos IMSS Laguna by the Mexican Social Security Institute of the state of Durango, and the following year it changed to its current name.

Jose Diaz Couder, IMSS head of social services in Gómez Palacio, was invited to participate in the tournaments despite the fact that he did not have a team.

When the IMSS sold its professional sports clubs, Salvador Necochea Sagi bought Santos Laguna.

William (the Clash) Galindo, Carlos González, Julio Cesar Armendáriz, Tomas Moreno and Fernando de la Rosa were notable players.

In 1988 Santos Laguna purchased the Puebla Angels, giving them Christian Saavedra, Wilson Graniolatti, Martin Zuniga and Miguel Herrera and a record of three wins, four draws and one loss.

Grupo Modelo made a strong investment in reinforcements, Antonio "El Turco" Apud, Daniel Guzmán, Olaf Heredia, Diego Silva, Héctor Adomaitis and Richard Zambrano who joined players coming from Second Division such as José Guadalupe Rubio and Pedro Muñoz.

Los Guerreros participated in the 1995 CONCACAF Champions Cup, and were eliminated in the first round by Deportivo FAS of El Salvador.

Chilean Cristian Montecinos reached the third league during the 1996 regular season, and Santos Laguna won their first First División title with new player Jared Borghetti.

Santos Laguna played poorly in the Invierno 1997 tournament, winning three games out of 17 and tied for last in the standings with Pumas UNAM and UAG Tecos.

The Warriors defeated Tauro FC of Panama by aggregate score of 5–3; in the next round, at home, Santos Laguna lost 3–2 overall to the U.S. champion Kansas City Wizards.

Finishing eighth overall, Santos Laguna defeated defending champion and leader Global America 5–4 at Azteca Stadium.

For the 2003 Apertura tournament (the club's 20th anniversary) reinforcements arrived in the form of Vicente Matias Vuoso and Sixto Peralta, Argentines who had played for Manchester City and Inter Milan.

The Warriors qualified for the playoffs, but were eliminated in the quarter-finals, Luis Fernando Tena's contract was not renewed, and he was replaced by Eduardo De la Torre.

The Warriors began 2004 well, qualifying for the Copa Libertadores by defeating Atlas Guadalajara 4–3, but were injured, inconsistent and tired in the Clausura.

Clausura 2009 was disastrous for the Warriors; coach Daniel Guzman was dismissed and replaced by Sergio Bueno, and the club's fortunes improved somewhat.

Cocca began Apertura 2011 with the support of the board and players, but was dismissed on September 3 and Eduardo Rergis became the interim coach.

After playing Monterrey to a 1–1 draw at Estadio Tecnologico, Santos Laguna won the second game 2–1 with goals by Daniel Ludueña and Oribe Peralta for the club's fourth title.

The Apertura 2012 featured Edgar Gerardo Lugo and rising defensive stars Monarcas Morelia and Oswaldo Alanis.

In the Clausura 2013, Portuguese manager Pedro Caixinha was hired based on a recommendation by former Real Madrid coach Jose Mourinho.

Daniel Ludueña and Christian Suarez were transferred to the Pachuca Soccer Club in exchange for Mauro Cejas, Nestor Calderon and promising Colombian Andres Renteria.

For the Apertura 2013, Santos sold Ivan Estrada to Pachuca and transferred Herculez Gomez, Gerardo Lugo and Aaron Galindo.

After defeating Atlante 3–1 in the latter half of the Apertura 2013, Santos Laguna secured a berth in the Copa Libertadores for the second time in their history.

[6] Los Guerreros sealed their elimination by losing 2-0 in the home leg after Ismael Blanco and Paolo Goltz scored for the Argentinian side.

[7] Following the two clashes in the tournament, several Lanús players were transferred to Santos Laguna in the latter months of the year, namely defender Carlos Izquierdoz, midfielder Diego "Pulpo" González and goalkeeper Agustín Marchesín.

In the Clausura 2018 tournament, under the management of former goalkeeper Robert Dante Siboldi, Santos Laguna earned twenty-nine points, tied with América and Monterrey, but placed fourth due to goal difference.

In the second leg, Santos Laguna played with ten players for most of the match as Jonathan Rodriguez was sent off in the 28th minute but managed to win 2-0 and advance to the semi-finals.

[11] In the final first leg, played in Estadio Corona, both Djaniny Tavares and Julio Furch netted for Santos Laguna, helping the team defeat Toluca 2-1.

Their uniform originated after the acquisition of Angeles de Puebla and their sponsorship by the Mexican Social Security Institute during the 1983–84 season.

[20] In 1991, when the club was in danger of relegation to the second division, Santos adopted their first team song: "Es hora de ganar", by Ricardo Serna.

Two years later, Chilean composer Martin Ibarreche Wilt Labarca was commissioned to write "Verdiblanco el corazon".