Stowe, the eldest of three sisters, was born Madeline Mora Stowe in Eagle Rock, a working-class suburb of Los Angeles, California. Her mother, Mireya (née Mora), immigrated from Costa Rica and came from a prominent family, and her father, Robert Stowe, a civil engineer, was a native of Oregon. Stowe's father suffered from multiple sclerosis.

At the age of ten, Stowe began taking piano lessons with the aim of becoming a concert pianist — and also as a way of not having to socialize with other kids. Her Russian-born music teacher Sergei Tarnowsky (he taught Vladimir Horowitz before immigrating to the US), had faith in her, teaching her from his deathbed. But when he died at the age of 96, she quit ("I just felt it was time to not be by myself anymore") — and at 18 she went on her first date. She then studied cinema and journalism at the University of Southern California. Not overly interested in her classes, Stowe volunteered to do performances at the Solaris, a Beverly Hil