Baltazar Saucedo Estrada, the Monterrey boss of the Zetas drug gang, was arrested while driving a stolen van containing stolen cash, four doses of cocaine and cannabis.
Police also arrested 41-year-old Ricardo Ramírez Hernandez. Both men were taken to the state attorney general's office for questioning.
Authorities allege that Estrada ordered the Aug. 25 firebombing of the Casino Royale after the owners refused to pay extortion money to the Zetas gang. The attack left 52 people dead and injured 10 others.
Just days after the attack, Mexican authorities detained five suspected members of the drug gang. All of the men confessed to being members of the criminal group and to being involved in the attack.
Security camera footage of the incident showed a group of armed men arriving at the casino in cars, carrying cans of liquid. The men could then be seen rushing out and speeding away a few minutes later, the building ablaze.
The Zetas were formed by deserters from Mexican special forces hired as hitmen for the Gulf cartel in the 1990s. In recent years, the group has become one of Mexico's most feared crime gangs.
The group has been blamed for kidnappings, extortion and murders in Mexico and beyond, including the massacre of 72 Latin American migrants in August 2010 in northeastern Mexico.