Mexican soldiers and federal agents arrested Damaso Lopez, the office of Mexico's attorney general announced via Twitter.
The US Treasury Department designated Lopez as a drug "kingpin" in 2013 for his role in Guzman's "narcotics trafficking activities ... And for playing a significant role in international narcotics trafficking."
As a senior Sinaloa cartel operative, Lopez is "responsible for multiple-ton shipments of narcotics from Mexico into the United States."
In 2001, Damaso Lopez also helped Guzman in his first of two escapes from a maximum security prisons.
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Guzman was recaptured in January 2016 and extradited to the United States a year later. Now 59, he is currently detained in Manhattan where he is awaiting trial.
Since Guzman's arrest top cartel operatives have engaged in a bloody struggle to control the group, resulting in a wave of violence in the western state of Sinaloa and nearby Baja California Sur.
Two weeks after Guzman was extradited his sons sent a hand-written letter to a reporter claiming that they had been victims of an ambush carried out by Damaso Lopez.
But when they reached the meeting place Lopez was absent, and instead his men tried to murder them.
The US Treasury Department has identified three of Guzman's adult sons -- Jesus Alfredo, Ivan and Ovidio -- as Sinaloa cartel members.
Lopez's arrest is the most recent blow to the cartel.
Last week, a Mexican judge sentenced Ines Coronel Barreras -- the father of Guzman's third wife, former beauty queen Emma Coronel -- to 10 years and five months prison for smuggling marijuana to the United States.