Bonnie Bartlett grew up in Moline, Illinois. Her father E.E. was a failed Shakespearean actor who became an insurance salesman. Her mother Carrie was a homemaker. At an early age, Bonnie became determined to fulfill her father's failed acting career. She went to Northwestern University to study acting. In her freshman year, she met fellow thespian William Daniels. Soon after graduation, the two were married and moved to New York to seek acting opportunities. She studied under Lee Strasberg and initially supported them.

In the 1950s she spent four years on the CBS soap Love of Life (1951) as Vanessa Raven. In 1961, their first child was born, but died within 24 hours due to complications in birth. This prompted the two to adopt two children later. Son Michael (b. 1964) is now an assistant director and stage manager in Los Angeles. Son Robert (b. 1966) is an artist and computer graphics designer in New York City. Bonnie was a stay-at-home mom through most of the 1970s, acting only occasionally in recurring roles, but rejuvenated her career in the early 1980s, most notably in the hit TV series St. Elsewhere (1982) and later in a recurring role in Boy Meets World (1993)