Lisa Kudrow was born in Encino, Los Angeles, California, the daughter of Nedra S. (née Stern), a travel agent, and Dr. Lee N. Kudrow (born 1933), a headache specialist and physician. Her ancestors emigrated from Belarus and lived in the village of Ilya, in the Minsk area, and her great-grandmother was murdered in the Holocaust. Kudrow was raised in a middle-class Jewish family and has an older sister, Helene Marla (born 1960), and an older brother, neurologist David B. Kudrow (born 1957). She is the niece of composer/conductor Harold Farberman. She took guitar lessons as a child and is left-handed. In 1979, at the age of 16, she underwent surgery which reduced the size of her nose.
After attending Portola Middle School in Tarzana, California, she graduated from Taft High School in Woodland Hills, Los Angeles. She received her B.A. in Biology from Vassar College, intending to follow in her father's footsteps and research headaches. Kudrow worked on her father's staff for eight years while breaking into acting, earning a research credit on his study on the comparative likelihood of left-handed individuals developing cluster headaches. For a time, Kudrow also worked as an anchor/reporter at KVII-TV, the ABC affiliate in Amarillo, Texas.