Westheimer was born Karola Ruth Siegel on June 4, 1928, in Wiesenfeld (near Karlstadt am Main), Germany, the only child of Orthodox Jews Irma (née Hanauer), a housekeeper and Julius Siegel, a notions wholesaler and son of the family in which Irma worked. She was given an early grounding in Judaism by her father, who took her regularly to the synagogue in Frankfurt, where they lived. In January 1939, she was sent to an orphanage in Switzerland by her mother and grandmother as part of the Kindertransport after her father had been taken by the Nazis. She stopped receiving her parents' letters in September 1941. In 1945, Westheimer learned that her parents had been killed in the Holocaust, possibly at the Auschwitz concentration camp.

Westheimer decided to emigrate to British-controlled Mandatory 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. Of this experience, she said, "I never killed anybody, but I know how to throw hand grenades and shoot." 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. Westheimer earned an M.A. degree in sociology from The New School in 1959 and an Ed.D. degree from Teachers College, Columbia University in 1970.

Westheimer became a naturalized U.S. citizen in 1965. She regained her German citizenship in 2012 through the German Citizenship Project that enabled descendants of Germans deprived of their citizenship during the Third Reich to reclaim their citizenship without losing the citizenship of their home country.

During the 1980s, "Dr. Ruth", became a household name and she made guest appearances on several network television shows, including The Tonight Show Starring Johnny Carson and Late Night with David Letterman. She also made frequent appearances on the syndicated revival of Hollywood Squares that ran from 1986 to 1989. In the 1990s, Westheimer appeared as herself in episode 89 of Quantum Leap, the episode title being "Dr. Ruth". She appeared on Tom Chapin's album This Pretty Planet, in the song "Two Kinds of Seagulls", in which she and Chapin sing of various animals that reproduce sexually. "It takes two to tingle", says the song. Dr. Ruth also appeared in several commercial advertisements, including a 1994 Honda Prelude ad, and an ad for Clairol Herbal Essences shampoo and body wash.

In 1984, Westheimer began hosting several television programs on the Lifetime (TV Network) and one in syndication. Her first show was Good Sex! With Dr. Ruth Westheimer, airing for a half hour at 10 pm on weeknights. This show was expanded in 1985 to a full hour and its name was changed to The Dr. Ruth Show. In 1987, she began a separate half hour syndicated series on many broadcast stations called, Ask Dr. Ruth, which was co-hosted by Larry Angelo. Dr. Ruth returned to the Lifetime network in 1988 with The All New Dr. Ruth Show, which was followed in 1989 by two teen advice shows called What's Up, Dr. Ruth? and a call-in show, You're on the Air with Dr. Ruth in 1990. In 1993, Westheimer and Israeli TV host, Arad Nir, hosted a talk show in Hebrew, titled Min Tochnit, on the newly opened Israeli Channel 2. The show was similar to her US Sexually Speaking show. The name of the show, Min Tochnit, is a play of words: literally "Kind of a program", but "Min" (מין) in Hebrew also means "sex" and "gender".

Westheimer has been married three times. She said that each of her marriages played an important role in her relationship advice, but after two divorces, it was her third marriage, to Manfred Westheimer, that was the "real marriage." This lasted until his death in 1997. She has two children, Miriam and Joel, and four grandchildren. In December 2014, Westheimer was a guest at an Orthodox Jewish wedding in the Bronx, NY. The groom, Rabbi Benjamin Goldschmidt, is the great-grandson of the woman who had helped rescue Westheimer from Nazi Germany. 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.

Between 2001 and 2007, Westheimer made regular appearances on the PBS Television children's show Between the Lions as "Dr. Ruth Wordheimer" in a parody of her therapist role, in which she helps anxious readers and spellers overcome their fear of long words. In the January 2009, the 55th anniversary issue of Playboy magazine includes Westheimer as #13 in the list of the 55 most important people in sex from the past 55 years. In October 2013, the play, Becoming Dr. Ruth opened Off Broadway. Actress Debra Jo Rupp played the role of Dr. Ruth. The play showcased the sex therapist's life from fleeing the Nazis in the Kindertransport and joining the Haganah in Jerusalem as a scout and sniper, to her struggles to succeed as a single mother coming to America. Eileen DeSandre played Dr. Ruth in the Virginia Repertory Theatre production of Becoming Dr. Ruth.

Westheimer has delivered commencement speeches at the Hebrew Union College seminary, Lehman College of the City University of New York, and, in 2004, at Trinity College, where she has been awarded honorary degrees. She also taught courses and seminars at Princeton and Yale, and was the guest speaker at the Bronx High School of Science in New York in commemoration of Yom HaShoah 2008. Westheimer 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 2002, she received the Leo Baeck Medal for her humanitarian work promoting tolerance and social justice.