Howard attended Brandeis University, but dropped out to marry. She worked at the Chicago Tribune and Chicago Daily News, and wrote for The New Republic, People, The Nation, and Boston Magazine. She penned a syndicated social commentary column "Margo" in the 1970s.

For several years, Howard wrote the Dear Prudence column featured in Slate magazine. Dear Prudence also was featured on National Public Radio and syndicated in more than 200 newspapers. In February 2006, she left the Dear Prudence column, and now pens a Dear Margo column for Women on the Web (wowowow.com), and for Creators Syndicate.

Her aunt, Pauline Esther Friedman Phillips, wrote the Dear Abby column. Although her mother and aunt were twin sisters and close while growing up, an intense rivalry developed between them because of their columns. In an echo of that rivalry, Howard has had several public differences with her cousin Jeanne Phillips, who took over the Dear Abby column when her mother became ill with Alzheimer's disease.

Howard has been married four times: first to John Coleman (1962—1967); second to Jules Furth (1972—1976); third to the actor Ken Howard (1977—1991); fourth (and currently) to Ronald Weintraub, a Boston cardiac surgeon. After her divorce from Howard, she retained the surname for professional use.

Howard has two daughters, Abra and Andrea. Her son is actor and director Adam Coleman Howard.