The Sinaloa OCG headed by Joaquín "El Chapo" Guzmán Loera and Ismael "El Mayo" Zambada, operates in about 17 Mexican states and approximately 40 countries. It is considered the largest and most powerful in Mexico, and amongst the most powerful around the world. Additionally, the organization has expanded operations throughout Latin America and is believed to be the largest purchaser of Peruvian cocaine. In the mid 2000s the Sinaloa organization was a dominant member of an alliance, known as "La Federacion," which included the Juárez and Valencia organizations.

In 2005 and 2006, the Sinaloan organization began developing armed enforcer groups to counteract an armed enforcer group (the Zetas) connected to the rival Gulf Cartel. The armed groups connected to Sinaloa were originally known as the Negros and Pelones, and were used to carry out paramilitary style operations. The Negros was led by U.S. born operative Edgar "La Barbie" Valdéz Villarreal.

In late 2007, Sandra Avila Beltrán, also known as "La Reina del Pacifico" or "Queen of the Pacific", was arrested and charged with money laundering, conspiracy to traffic drugs and organized crime. Avila had been vital to developing and maintaining relationships with Colombian drug trafficking organizations allowing the Sinaloa DTO to sell cocaine in the U.S. market. Due to increased pressure on its operations, the Sinaloan's expanded into other illicit activities and now control sizable percentage of human smuggling routes into Arizona.

By 2008 the Federación began to splinter into separate groups including the Vicente Carrillo Fuentes (or Juárez) organization, the Arrellano Felix Organization, and the Beltran Leyva Organization which included elements of the Negros (with La Barbie) and the Pelones. In the breakup, the Sinaloa organization managed to maintain its cocaine smuggling routes from South America to the United States and emerged as Mexico's single most powerful trafficking organization believed to control as much as 45% of Mexico's drug trade.

Since 2008 the Sinaloa organization has been locked in a deadly battle for control of the Ciudad Juárez plaza, or territory, traditionally a stronghold for the Juárez organizations also known as the Vicente Carrillo Fuentes (VCF) cartel. The conflict between the two organizations is centered in Ciudad Juárez, which has become the most deadly city in the world by most estimates. While the conflict is largely about access to the U.S. market via the Juárez-El Paso corridor, there are also elements of personal rivalry and vendetta between the organizations that help explain the sustained and brutal nature of the killings.

By most estimates, the Sinaloa cartel appears to have the upper hand in the conflict over the Ciudad Juárez plaza. Sinaloa has spread its influence and control into small towns along the Rio Grande formerly under Juárez control. Despite increased efforts by the Sinaloa organization to encircle the Juárez organization, Juárez continues to have strength in the city itself where its base of operations have allowed it to develop a strong local presence and become deeply imbedded in local government and law enforcement.

In early 2010, the Sinaloa organization began forming a strategic, possibly short-term, alliance with its former rival, the Gulf OCG, as well as with "La Familia Michoacana," in an effort to wrest control of certain plazas from the Zetas, who recently broke off from the Gulf cartel. This new pact came as the Sinaloa organization began to expand its presence in Baja California, as well as in the region known as "El Triángulo Dorado" composed of the states of Sinaloa, Durango and Chihuahua.

On July 29, 2010 the Sinaloa organization was dealt a major blow to its leadership when Ignacio "Nacho" Coronel, the number three figure behind "El Chapo" and "El Mayo", was killed in a shootout with the Mexican military in Jalisco.