The league wanted a longer penalty for the third-year linebacker, but the sides agreed to less than half the season.
Miller's suspension will begin Aug. 30, the day after Denver's final preseason game. He is eligible to return for Denver's seventh game, Oct. 20 at the Indianapolis Colts. The suspension will cost Miller more than $800,000 of the nearly $2.3 million he's scheduled to make this season.
The suspension also will cost Miller more than $1.2 million in bonus money, per a rule in the collective bargaining agreement on substance-abuse suspension, a source confirmed to ESPN. The forfeiture of the money that was paid out more than two years ago had been earlier reported by ProFootballTalk.com.
After being notified of the decision, Miller released a statement saying "although my suspension doesn't result from a positive test, there is no excuse for my violations of the rules."
"I made mistakes and my suspension has hurt my team, Broncos fans, and myself," he said. "I am especially sorry for the effect of my bad decisions on others. I will not make the same mistakes about adhering to the policy in the future. During my time off the field, I will work tirelessly and focus exclusively on remaining in peak shape. I look forward to contributing immediately upon my return to the field and bringing a championship back to the people of Denver."
The NFL has two drug policies -- one that covers use of performance-enhancing substances and the "Policy and Program for Substances of Abuse" that applied to Miller's case.
There are ways to violate the drug policy without necessarily testing positive. They include missing a test, refusing to test, tampering with tests or giving a diluted urine sample.
"I don't know if that was confidence as much as it was wishful thinking," coach John Fox said. "I think we all tend to look at the glass half full instead of half empty. But now the reality is there and I'm kind of glad we've gotten to where it is finalized."
The Broncos had been operating throughout the preseason as if Miller would be with them for their regular-season opener Sept. 5.
"Von has acknowledged making some mistakes in the past and is now being held accountable under the policies the league has in place," Fox said. "While it's very disappointing that we will be without him for the start of the season, we will support him as a football team and organization. All of us will stand by Von and help him however possible as he continues his personal growth off the field."
Fox said Miller will play in Saturday's preseason game against the the Rams at Sports Authority Field at Mile High.
Broncos executive vice president of football operations John Elway also acknowledged Miller's situation.
"We're frustrated with what's happened, disappointed in Von,'' Elway said. "But I think the way I've looked at this, and will continue to look at this, is the decision that's come down we live with that decision. And what I'd like to do is whatever we have to do to prevent any other situations. Whatever we have to do as an organization to try and help Von we want to be able to do.'
"Put aside the fact that he's a good football player. Him as a person, if we can get him help to help him take that next step in the maturation process, we want to do that.'"
Now, a team with Super Bowl aspirations must scramble to replace its best player on defense, the second pick of the 2011 draft, who was the NFL Defensive Rookie of the Year in 2011 and runner-up last season for the league's Defensive Player of the Year.
Likely to take his spot at the rush linebacker position is Shaun Phillips, a 10-year veteran the Broncos signed in free agency during the offseason.
Miller, meanwhile, has a number of issues pending before his return, first of which is keeping the trust of his teammates, who have steadfastly backed him during a summer filled with turmoil.
"Has not changed," Peyton Manning said Tuesday, before word of the six-game suspension became official. "There's been a lot of noise and speculation. But Von is one of our teammates. He's part of the family, and I certainly have his back as his teammate and I know that all the players do and the organization does."
Miller also must clear up his recent arrest for failing to appear in court for traffic violations. News of the arrest came as Miller was deep in negotiations with the league and the union about his case, about which he repeatedly insisted he had "done nothing wrong."
Manning, of course, is the lynchpin of a team built to win the Super Bowl now.
But it's Miller whom Elway recently called the most talented football player he'd ever seen.
The linebacker will be on the sideline for the season opener against Baltimore, then at the New York Giants, home against Philadelphia and Oakland, at Dallas and home against Jacksonville. His return coincides with Manning's first game in Indianapolis since he last put on a Colts uniform.
While Miller's gone, the Broncos will shuffle at the linebacker position.
Miller has been practicing with the first team, though a window into the team's thinking came last Thursday, when he missed practice while he met with lawyers. Nate Irving, normally a middle linebacker, played on the strong side, and Phillips filled in at Miller's spot. Middle linebacker Stewart Bradley hurt his left wrist Saturday night, throwing another wrench into the ever-developing contingency plans.
The Broncos, perhaps preparing for Miller's expected absence, signed veteran linebacker Paris Lenon on Tuesday. The 35-year-old Lenon had 103 tackles for the Arizona Cardinals last season. Lenon, who has also played for the Green Bay Packers, Detroit Lions and St. Louis Rams, has 810 tackles, 12 sacks, 10 forced fumbles and five interceptions in 175 career games. He signed after working out for the team earlier Tuesday.
Information from ESPN.com's Jeff Legwold and The Associated Press was used in this report.