During an interview with television journalist Barbara Walters, she commented on the Supreme Court ruling on abortion, saying it was time to bring abortion out of the backwoods and put it in the hospitals where it belonged. Less than a year after being appointed vice president, Gerald Ford became president of the United States when Richard Nixon resigned. On August 9, 1974, Ford took on a new role-first lady. In her 1978 autobiography, Ford described her sudden fame: "I was an ordinary woman who was called onstage at an extraordinary time. I was no different once I became first lady than I had been before. But, through an accident of history, I had become interesting to people."

As first lady, Ford became known for her candor and forthrightness. She gained the public's admiration when, shortly after moving into the White House, she was diagnosed with breast cancer and underwent a mastectomy. At the time, cancer and mastectomy were subjects people didn't discuss publicly. Ford explained her reason for going public in an interview in Ms. magazine in 1984: "We were in a position where my husband had been sworn into office during a very, very difficult time. There had been so much cover-up during Watergate that we wanted to be sure there would be no cover-up in the Ford Administration. So rather than continue this traditional silence about breast cancer, we felt we had to be public." The American people reacted with admiration. Breast detection clinics opened nationwide and women lined up for screenings. Ford championed many other causes as first lady. She campaigned for the Equal Rights Amendment, the proposed Constitutional amendment that would have guaranteed equal rights to women. She encouraged the president to appoint women to high-level positions-secretary of Housing and Urban Development and ambassador to Great Britain. Ford was an advocate for the arts. She persuaded her husband to present the Presidential Medal of Freedom to Martha Graham. Ford remained a friend of Graham's until her death in 1991. Ford also worked for social causes. She supported Washington's Hospital for Sick Children, the Heart Association, Goodwill Industries, the Cancer and Arthritis foundations and No Greater Love, an organization which assisted children of soldiers lost or missing in action. Ford's outspokenness continued to gain attention. During a television interview with Morley Safer on Sixty Minutes, she repeated her support for the right of pregnant women to decide whether they wished to have an abortion. She also raised no objections to young people of opposite genders cohabiting before marriage.