He was born in Toledo, Ohio. He received his BA from Yale University in 1935, and his Ph.D. from Princeton University in 1938, where he was advised by Henry Norris Russell. He is one of the key figures of 20th century physics, who helped lay down the fundamentals of the physics of plasmas and the astrophysics of the interstellar medium. He founded the Princeton Plasma Physics Lab, and in 1946, he envisioned what would eventually become the Hubble Space Telescope. One of his more famous students was George Field. Spitzer died in Princeton, New Jersey.
The NASA's Spitzer Space Telescope is named after him. It studies the infrared sky from an Earth trailing orbit.