She died of congestive heart failure at her home in California, the Reagan library said in a statement.
She will be buried alongside her husband, former US president Ronald Reagan, at the Ronald Reagan Presidential Library.
Born in New York City on 6 July 1921, Mrs Reagan was an actress when she married the future president in 1952.
Her marriage lasted for 52 years before Mr Reagan's death in 2004.
She served as first lady between 1981 and 1989.
President Barack Obama and current first lady Michelle Obama said in a statement: "Nancy Reagan once wrote that nothing could prepare you for living in the White House.
“She was right, of course. But we had a head start, because we were fortunate to benefit from her proud example, and her warm and generous advice. Our former first lady redefined the role in her time here."
And her stepson, Michael Reagan, tweeted: "I am saddened by the passing of my step mother Nancy Reagan...She is once again with the man she loved. God Bless..."