It is a second ban this year for the second-year professional, who missed the first four games after pleading guilty to a drink-driving charge and was placed in the league's substance-abuse programme as a result.
An NFL statement reproduced on the Jaguars' website read: "Justin Blackmon of the Jacksonville Jaguars has been suspended indefinitely without pay for violating the NFL Policy and Program for Substances of Abuse.
"Blackmon's suspension begins immediately. He will be eligible to apply for reinstatement prior to the start of the 2014 season."
In a statement released to ESPN by Blackmon's agent, the 23-year-old said: "I am determined to overcome the issues that have resulted in this situation, and I truly appreciate the support that the Jaguars and my agent have shown me.
"I will address these matters with the type of intensity I usually direct toward my on-field play so that I can be ready to be a productive member of the team and community next season.
"I am truly sorry to (team owner Shahid) Khan, my team-mates and coaches and to the Jaguars fans for the impact of my situation on the team as well as to my family and friends and those that have been there for me during these challenging times. Nobody is more disappointed with all of this than me."
The Jaguars traded up to select Blackmon from Oklahoma State College with the fifth overall pick of the 2012 draft.
While with the Cowboys, Blackmon was a two-time winner of the Biletnikoff Award as the nation's top college receiver, a feat only previously achieved by the San Francisco 49ers' Michael Crabtree when with Texas Tech.
Jaguars general manager David Caldwell told their website: "All of us who are a part of the Jaguars family care very deeply about Justin and his well-being. That said, he must be held accountable and accept the consequences announced today by the NFL.
"His suspension will provide him the opportunity to receive the attention and professional treatment necessary to overcome his challenges, and we will support him during this time.
"The Jacksonville Jaguars will evaluate Justin's status once he has successfully met the criteria to be considered for reinstatement to the league."