The singer's son, Teddy Pendergrass II, said his father died at Bryn Mawr Hospital in suburban Philadelphia. The singer underwent colon cancer surgery eight months ago and had "a difficult recovery," his son said.
"To all his fans who loved his music, thank you," his son said. "He will live on through his music."
Pendergrass suffered a spinal cord injury and was paralyzed from the waist down in the 1982 car accident. He spent six months in a hospital but returned to recording the next year with the album "Love Language."
He returned to the stage at the Live Aid concert in 1985, performing from his wheelchair.
Pendergrass later founded the Teddy Pendergrass Alliance, an organization whose mission is encourage and help people with spinal chord injuries achieve their maximum potential in education, employment, housing, productivity and independence, according to its Web site.