Piper's agent, Jay Schachter, said in a statement that "Rod passed peacefully in his sleep last night."
"I am shocked and beyond devastated," Schachter said. "He was an icon, a legend, an amazing man and a true friend." In 2006, the WWE announced that Piper had been diagnosed with Hodgkin's lymphoma and would receive treatment.
Piper, whose real name is Roderick George Toombs, joined World Wrestling Entertainment in 1984; before that he wrestled in the NWA.
Piper was known for his on-air feud with Hulk Hogan, and the wrestling entertainment company said Piper began his career as "one of the most-hated villains ever to step between the ropes."
Piper and "Mr. Wonderful" Paul Orndorff took on Hogan and Mr. T in the first-ever WrestleMania. WWE calls the bout "one of the marquee main events in its history."
Piper was inducted into the WWE Hall of Fame in 2005. He was also named one of the WWE's "Top 50 Villains.
"Roddy Piper was one of the most entertaining, controversial and bombastic performers ever in WWE, beloved by millions of fans around the world," WWE Chairman & CEO Vince McMahon said in a statement. "I extend my deepest condolences to his family."
Piper starred in the 1988 John Carpenter cult classic sci-fi film "They Live."
Carpenter said Thursday he was "devastated" by the news. "He was a great wrestler, a masterful entertainer and a good friend," Carpenter said in a post on Facebook.
Piper is survived by his wife, Kitty, and their four children.