The U.S. Anti-Doping Agency announced the verdicts of an American Arbitration Association panel against Bruyneel and two medical staff, completing its lengthy investigation which saw Armstrong banished from cycling in 2012.
Bruyneel "was at the apex of a conspiracy to commit widespread doping on the (U.S. Postal Service) and Discovery Channel teams spanning many years and many riders," USADA said in a statement.
Team doctor Pedro Celaya and trainer Jose "Pepe" Marti will serve eight-year bans.
Bruyneel claimed he, Armstrong and the others have been made scapegoats for an era when doping was "a fact of life" in cycling.
"I do not dispute that there are certain elements of my career that I wish had been different," Bruyneel said in a statement. "However, a very small minority of us has been used as scapegoats for an entire generation."
Armstrong's lawyer, Tim Herman, declined to comment on the case to The Associated Press.
As a Belgian national, Bruyneel questioned USADA's right to prosecute him and said he would consider appealing to the Court of Arbitration for Sport in Lausanne, Switzerland.
Bruyneel, Celaya and Marti faced charges including trafficking and administering doping products and methods, including EPO, blood transfusions, testosterone, human growth hormone and cortisone.
The ruling said Bruyneel encouraged his riders to cheat, and Levi Leipheimer, one of eight former Armstrong teammates who gave evidence, testified to the director's "integral role" managing the doping program.
"Specifically, Mr. Leipheimer stated that Mr. Bruyneel 'was the boss; people who took actions only did so from his instructions,'" the AAA stated in its 112-page published ruling.
The verdicts followed a four-day hearing in London last December before a three-member AAA panel.
"The panel found that Bruyneel himself 'profited considerably from the successes of the teams and riders he managed during the relevant period,'" the USADA statement said.
Bruyneel refused to testify and "presented no fact witnesses on his own behalf," USADA said.
Marti also refused to testify, while Celaya was cross examined and found by the panel not to be a credible witness, the ruling said.
Bruyneel is banned from working in all sports to June 11, 2022. Celaya's and Marti's sanctions end on June 11, 2020. The AAA panel increased the standard four-year bans for trafficking or administering doping products because they were part of a wider conspiracy.
The sanctions date from June 2012 when USADA accused Armstrong and his teams of widespread doping.
Armstrong was stripped several weeks later of all of his post-August 1998 race results, including all seven Tour de France titles, and banned for life by USADA. Doctors Michele Ferrari and Luis Garcia del Moral also did not challenge USADA's findings and lifetime bans.
In October 2012, USADA published its detailed verdict with hundreds of pages of evidence documenting the doping conspiracy, including witness statements from several Armstrong teammates.
At Bruyneel's closed-door hearing in London, 17 witnesses provided testimony in person or by video link, including eight cyclists: Michael Barry, Tom Danielson, Tyler Hamilton, George Hincapie, Floyd Landis, Levi Leipheimer, Christian Vande Velde and David Zabriskie.
"Each witness testified that Mr. Bruyneel organized, assisted, and encouraged the use of doping for riders on those teams," the panel ruling stated.
The panel said it did not consider testimony by Hamilton and Landis, who perjured themselves in previous cases examining their own doping, and because Landis has a financial conflict of interest with his whistleblower suit.
Celaya was doctor for the USPS/Discovery Channel team from 1997-98 and from 2004-07. He returned to work with Bruyneel at RadioShack Nissan Trek as the USADA investigation continued.
Marti worked for Bruyneel from 1999 to 2007 at USPS and Discovery Channel, and then with the Astana team.
USADA said that Marti worked "most recently" for the Denmark-based Team Saxo Bank-Tinkoff Bank, which is managed by 1996 Tour winner Bjarne Riis. Its star rider is Alberto Contador, who won the Tour de France in 2007 and 2009 riding for teams directed by Bruyneel, then was stripped of the 2010 title after testing positive for clenbuterol.
Contador was mentioned in Marti's defence to try to rebut Leipheimer's testimony that the Spanish trainer extracted blood from the American rider after a June 2007 race in France.
"Mr. Marti also argued that he could not have been present for the 2007 blood transfusion after the Dauphine Libere because he was training with Alberto Contador at that time," said the panel's ruling, which dismissed the alibi for lack of supporting evidence.
Associated Press writer Jim Vertuno in Austin, Texas, contributed to this report