Donald Henri Grusin was born April 22, 1941, and grew up in Littleton, Colorado, the son of a classical violinist who had emigrated from Latvia. Rather than pursue music first, he earned a bachelor's degree in sociology and a master's degree in economics from the University of Colorado Boulder, and spent the early 1970s teaching economics, first as a professor in Guadalajara, Mexico, then at Foothill College in California. In 1975, Quincy Jones invited him to tour with his band, and Grusin left academia for a career in music.

He is the younger brother of pianist and producer Dave Grusin, co-founder of GRP Records, whose own career is covered in full in his JazzProfiles.com profile. Don Grusin built a substantial career of his own as a keyboardist, composer, and record producer, releasing his self-titled debut album in 1981 and a long, steady catalog since, including 10K-LA (1984), Sticks and Stones (1988), Zephyr (1991), Native Land (1993), Old Friends and Relatives (1996), Laguna Cove (1998), and The Hang (2004), among many others, often drawing on Latin jazz influences across his catalog (Tudo Bem!, 1991; Trans Atlántica, 2012).

Don Grusin's late entry into professional music, arriving via an economics career rather than formal conservatory training, produced a catalog that leans toward warm, melodic contemporary jazz with recurring Latin jazz influences, distinct from though clearly adjacent to his brother's more widely known GRP Records-era work.