Christened Anne Frances by her parents, she was quickly nicknamed Nancy by her mother and used that name throughout her life. Her father, Kenneth Robbins, a salesman, and her mother, Edith Luckett Robbins, an actress, separated when Nancy was very young. Edith immediately resumed her acting career and began traveling a great deal, leaving Nancy in Bethesda, Maryland, where she was raised by Edith's sister and brother-in-law. Nancy saw little of her mother over the next five years and had no contact with her father, and her parents divorced in 1928.

In 1929, when her mother married Loyal Davis, a wealthy Chicago neurosurgeon, Nancy went to live with the couple. Davis eventually adopted her, and she assumed his last name. After graduation from the Chicago Latin School for Girls, she enrolled at Smith College in Massachusetts and majored in drama. Her mother's theatre friends often visited the Davis household in Chicago, fueling Nancy's interest in the stage. After graduation in 1943 and a brief stint working at a department store in Chicago, she turned to acting. Her mother's contacts helped her obtain a job with a touring company and then a role on Broadway. By 1949 she was working in Hollywood, and she eventually made 11 movies, including East Side, West Side (1949), Shadow on the Wall (1950), and Hellcats of the Navy (1957), in which she starred with Ronald Reagan.

During the 1950s Ronald's political views became more conservative. Although a Democrat at the time, he supported the presidential candidacies of Dwight D. Eisenhower (Eisenhower, Dwight D.) in 1952 and 1956 and Richard Nixon (Nixon, Richard M.) in 1960. After switching his party affiliation to Republican in 1962, he became cochair of California Republicans for Barry Goldwater (Goldwater, Barry) in 1964. Many people credit the influence of Nancy and her stepfather for Ronald's shift to the right.

Ronald launched his political career in 1966, winning election as governor of California by defeating incumbent governor Edmund G. Brown, Sr., by one million votes. During her eight years as the governor's wife, Nancy developed the skills that later served her in the White House, but she also aroused controversy. She was criticized for her circle of wealthy, glamorous friends and her expensive, stylish clothing. Intensely protective of her husband, she also ran into conflict with journalists who wrote negatively about him and with staff members who, she felt, overscheduled him. Although she did not voice her opinions publicly and occasionally attempted to play down her influence, her husband and his staff took her seriously. When Ronald won the presidency in 1980, it was generally agreed that Nancy was one of his most trusted advisers.

Despite her protests, the view persisted that Nancy influenced her husband in personnel matters and on important issues such as arms control and relations with the Soviet Union. When television cameras caught her whispering answers to reporters' questions in the president's ear, speculation increased about her role. While Ronald convalesced after major surgery in 1985, The New York Times concluded that a triumvirate was in charge at the White House: the president, his chief of staff, and the first lady. A year later, the paper described how she had “expanded the role of First Lady into a sort of Associate Presidency.” This perception was bolstered by the accounts of former staff members, including Donald Regan, the president's chief of staff, who publicly blamed her for his firing in 1987. Regan also claimed that Nancy insisted that the president's schedule take into account her astrologer's predictions and warnings. In her memoirs, she admitted having access to her husband—“For eight years I was sleeping with the president, and if that doesn't give you special access, I don't know what does”—but insisted that Regan had exaggerated her influence: “Believe me, if I really were the dragon lady that 【Regan】 described in his book, he would have been out the door many months earlier.”

The Reagans left the White House in January 1989, returning to their Bel Air estate in California, and Nancy continued her antidrug work under the auspices of the Nancy Reagan Foundation. After her husband was diagnosed with Alzheimer disease in 1994, she devoted all her time to caring for him and made very few political appearances.