Harley Quinn Smith was born in Red Bank, New Jersey, to Jennifer Schwalbach and Kevin Smith. At the age of two, Smith and her family moved to Los Angeles. Smith had intentions to become a professional bass guitarist, but later fell in love with acting.
She has been seen in several films, including in Yoga Hosers (2016), which she stars in opposite Lily-Rose Depp. Smith made her acting debut in Jay and Silent Bob Strike Back (2001) and had cameos in the drama film, Jersey Girl (2004), and in the comedy film, Clerks II (2006).