The clothing and footwear company said Wednesday that it was terminating Armstrong's contract "with great sadness."
"Nike does not condone the use of illegal performance enhancing drugs in any manner," it said in a statement.
Armstrong said Wednesday, just minutes before the announcement from Nike, that he was stepping down as chairman of his Livestrong cancer-fighting charity so that the organization can steer clear of the whirlwind surrounding its founder.
A representative for Armstrong could not be immediately reached for comment.
Nike Inc., based in Beaverton, Ore., said it plans to continue its support for Livestrong. Anheuser-Busch and the sunglasses company Oakley have already pledged ongoing support for the organization.
The U.S. Anti-Doping Agency released a massive report last week detailing allegations of widespread doping by Armstrong and his teams when he won the Tour de France seven consecutive times from 1999 to 2005.
The 41-year-old Armstrong, who overcame life-threatening testicular cancer, retired from cycling a year ago. He announced in August that he would no longer fight the doping allegations that have dogged him for years.
Nike's courting of top celebrity athletes is well known, as are the inherent risks companies assume when doing so.
After Tiger Woods ran his SUV over a fire hydrant in November 2009, eventually bringing to light his infidelities, Accenture, AT&T Inc. and Gatorade cut ties with him. But EA Sports and Nike stood by the golfer.
Nike signed NFL quarterback Michael Vick to a contract during his rookie year in 2001, but ended that pact in August 2007 after he filed a plea agreement admitting his involvement in a dogfighting ring. Vick spent 21 months in prison.
Nike re-signed Vick, who plays with the Philadelphia Eagles, in July 2011. The company said at that time that it didn't condone Vick's actions, but was supportive of the positive changes he had made to better himself off the field.
Shares of Nike edged slightly higher in early trading.