Bryant's suspension, which is without pay, begins immediately, the NFL said. He was scheduled to earn $600,000 in 2016.
"He is at a crossroads of his professional life, and he needs to understand significant changes need to occur in his personal life if he wants to regain his career as a Pittsburgh Steeler." Steelers GM Kevin Colbert on Martavis Bryant
General manager Kevin Colbert said the Steelers "are very disappointed" with Bryant for his suspension.
"He is at a crossroads of his professional life, and he needs to understand significant changes need to occur in his personal life if he wants to regain his career as a Pittsburgh Steeler," Colbert said.
"We are hopeful that Martavis will take the necessary steps to develop the discipline in his personal life to become a successful player and a good teammate."
Bryant decided not to appeal the suspension. His agent Tom Santanello had said on Saturday that Bryant had planned to appeal.
The suspension is related to NFL drug testing, a source told ESPN.
Last year, the NFL suspended Cleveland Browns receiver Josh Gordon for a minimum of one year for violating the substance abuse policy. He appealed the suspension, but the ruling was upheld by an arbitrator. Gordon has applied for reinstatement but remains suspended.
Another of his agents, Brian Fettner, told USA Today Sports that Bryant, who served a four-game suspension last season for violating the league's substance abuse policy, is fighting depression and plans to enter rehab Sunday for evaluation.
"We're all stunned, me included," Fettner told USA Today Sports. "We clearly miscalculated the issue. His isn't a party issue. It's a coping issue and a depression issue, and he's got to take care of it.
"This is the biggest cry for help I've ever seen, and that hurts. It hurts us to see. He's 24 years old, and he's got to get right, whatever it is. If you talk to anybody's family that has depression, they will be talking about these same things -- the [despondence], the withdrawal, the head-in-the-sand despair -- just trying to cope."
After returning from his four-game suspension, Bryant had a productive 2015 season for the Steelers, hauling in 50 receptions for 765 yards and six touchdowns in 11 games.
Pittsburgh's decision to sign receiver Darrius Heyward-Bey to a three-year extension was a direct result of Bryant's potential absence in 2016, a source told ESPN. The Steelers likely would have re-signed Heyward-Bey, but if not for the possibility of Bryant's absence, Heyward-Bey wouldn't have had the leverage to earn a three-year deal. Pittsburgh also signed tight end Ladarius Green to a four-year, $20 million deal.
ESPN's Jeremy Fowler contributed to this report.