Blackmon missed the first five games of the season after breaking the policy last season and as a result of the second infraction has been banned for the year.
The 23-year-old will now have to apply for reinstatement to the NFL to be able to play in the 2014 season.
The NFL said in a statement: "Justin Blackmon of the Jacksonville Jaguars has been suspended indefinitely without pay for violating the NFL Policy and Programme 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."
Jaguars general manager David Caldwell told the club's official 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."
The Jaguars are 0-8 in their season after week eight.