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."
Reeve told interviewer Kathie Lee Gifford she wanted to get back on Broadway, where she had performed in the flop "More To Love" in 1998. She was performing in the Broadway-bound play "Brooklyn Boy" in California when she had to streak home to reach her husband's bedside before he died. She gave up the role for the New York run.
She also appeared Off-Broadway and regionally, and in New York-based television shows.
Reeve was upbeat during the "Entertainment Tonight" interview, Carl said.
"She always was a very, very positive individual, but I think that, at this point, she was fully believing that she was going to fight this and that she could win the battle," Carl reports.
Dana Reeve was a constant companion and supporter of her husband during his long ordeal and his work for a cure for spinal cord injuries.
"With Chris, she gave voice to a movement to find life-saving cures and promote medical research, and when she lost her inspiration and love she didn't stop the fight," said Sen. John Kerry, D-Mass., in a statement. "She was an inspiration to me and to us all. Chris was America's superhero, and Dana became our hero, too."
She was chairwoman of the Christopher Reeve Paralysis Foundation, which funds research on paralysis and works to improve the life of the disabled. To date, it has awarded $55 million in research grants and $7.5 million in quality of life grants.
Reeve also served on the boards of The Williamstown Theatre Festival, The Shakespeare Theatre of New Jersey, TechHealth, and The Reeve-Irvine Center for Spinal Cord Research and as an advisory board member to the National Family Caregivers Association.
"We celebrate her, and we're so sad to lose her," Williamstown's artistic director Roger Rees told CBS Radio News. "She was an extraordinary example of what companionship and love and vitality and extremely wonderful talent can do in this business."
The Reeves first met while both were acting at Williamstown.
She received numerous awards for her work, including the Shining Example Award from Proctor & Gamble in 1998, an American Image Award from the AAFA in 2003. In 2005, the American Cancer Society named her Mother of the Year.
"She talked about how resilient children can be" in the ET interview, Carl said. "She said that Will has had better or worse. He has lived with that since he was three" when his father had the horse-riding accident.
"Our thoughts and prayers are with her son Will and the entire Reeve family," said former president Bill Clinton and his wife, Sen. Hillary Rodham Clinton (D-N.Y.). "We especially want Will to know that his mother's determination and bravery inspired us and so many others, and we will continue to work toward the causes and goals she championed."
Reeve is also survived by her father, Dr. Charles Morosini, and sisters Deborah Morosini and Adrienne Morosini Heilman.
No funeral plans were announced. The family said donations could be made in Dana Reeve's memory to the Christopher Reeve Foundation in Short Hills, N.J.