Reeve died late Monday at Memorial Sloan-Kettering Medical Center of lung cancer, said Sean Dougherty, a spokesman for the foundation. Survivors include a teenage son, Will, and two stepchildren, Matthew and Alexandra.
"On behalf of the entire board of directors and staff of the Christopher Reeve Foundation, we are extremely saddened by the death of Dana Reeve, whose grace and courage under the most difficult of circumstances was a source of comfort and inspiration to all of us," Kathy Lewis, president and CEO of the foundation, said in a statement.
Comedian Robin Williams, a longtime friend, said of Reeve's death: "The brightest light has gone out. We will forever celebrate her loving spirit."
Williams and Christopher Reeve were roommates at The Julliard School.
Reeve had announced on Aug. 9 that she had lung cancer.
Christopher Reeve, the one-time Hollywood "Superman" turned activist for spinal cord research after a horse-riding accident in 1995, died Oct. 10, 2004.
Dana's mother died shortly afterward. Then in August, Dana announced she had inoperable cancer.
"Just when you think you're coming out and you think, 'OK, I see the light at the end of the tunnel,' then I got this diagnosis in the summer," Dana Reeve said at a cancer fundraiser in New York last year.
"While it is the more the more unusual scenario that someone who never smoked would develop lung cancer, 10 to 15 percent of the cases do occur in non-smokers," says CBS News health correspondent Emily Senay. "One of the major problems is, by the time it's detected, it's often quite far advanced."
"What I didn't know is that lung cancer is the number-one cancer. We're always looking for breast and ovarian and uterine, and I'm a non-smoker, and I live in the country, so I think 'I'm good,' so I was completely shocked," she told "Entertainment Tonight" interviewer Kathie Lee Gifford. ("ET" is also part of CBS, Inc.)
Before the interview, she sang at the Madison Square Garden ceremony retiring the number of former New York Rangers captain Mark Messier on Jan. 12, 2006.
"Dana enjoyed it (the performance)," ET reporter Jann Carl told CBS Radio News. "She had always been singing and acting, and Dana was very, very eager to get back to work."