Westheimer was born Karola Ruth Siegel in Wiesenfeld (near Karlstadt am Main), Germany, the only child of Orthodox Jews Irma (née Hanauer) and Julius Siegel. In January 1939, she was sent to Switzerland by her mother and grandmother after her father was taken by the Nazis. There she came of age in an orphanage, and stopped receiving her parents' letters in September 1941. In 1945, Westheimer learned that her parents had been murdered in the Holocaust, possibly at the Auschwitz concentration camp.
Westheimer decided to emigrate to the British Mandate of Palestine. There, at 17, she "first had sexual intercourse on a starry night, in a haystack without contraception." She later told The New York Times that "I am not happy about that, but I know much better now and so does everyone who listens to my radio program." Westheimer joined the Haganah in Jerusalem. Because of her diminutive height of 4 ft 7 in (1.40 m), she was trained as a scout and sniper. Westheimer was seriously wounded in action by an exploding shell during the Israeli War of Independence in 1948, and it was several months before she was able to walk again.
In 1950, Westheimer moved to France, where she studied and then taught psychology at the University of Paris. In 1956, she immigrated to the United States, settling in Washington Heights, Manhattan.  She still lives in the "cluttered three-bedroom apartment in Washington Heights where she raised her two children and became famous, in that order." Because of the two synagogues she belongs to, the YMHA she was president of for three years, and a "still sizable community of German Jewish World War II refugees," she remains in the neighborhood. She speaks English, German, French, and Hebrew.
She earned a master's degree in sociology from The New School and an Ed.D. from Teachers College, Columbia University. She completed post-doctoral work in human sexuality at New York-Presbyterian Hospital, training with pioneer sex therapist Helen Singer Kaplan.
Westheimer has written several books on human sexuality, including Dr. Ruth's Encyclopedia of Sex and Sex for Dummies. The full version of Dr. Ruth's Encyclopedia of Sex is currently available online.
Westheimer has given commencement speeches at the Hebrew Union College seminary, Lehman College of the City University of New York, and, in 2004, at Trinity College. She has also taught courses and seminars at Princeton and Yale.
Westheimer was the guest speaker at the Bronx High School of Science in New York in commemoration of Yom HaShoah 2008. She spoke about her life story and the audience of 500 sang "Happy Birthday" in honor of her 80th birthday. At the ceremony she received an honorary Bronx High School of Science diploma. In 2008 she was awarded an Honorary Doctorate by Westfield State College.
In 2002, she received the Leo Baeck Medal for her humanitarian work promoting tolerance and social justice.
Westheimer has been married three times. Her third marriage, to Manfred Westheimer, lasted until his death in 1997. She has two children, Miriam and Joel, and several grandchildren.