Leonardi was born in Philadelphia in 1957, and grew up in Haverhill, Massachusetts. He graduated from Dartmouth College in 1979. His professional career began in 1980.
His work is characterized by his use of dynamic figure work (particularly evident in his Spider-Man work), and panel composition that often involves shifting of the camera eye and perspective.
His well-known works include various sporadic fill-in issues of The Uncanny X-Men and The New Mutants, as well as runs on Cloak and Dagger, Spider-Man 2099, Nightwing, Batgirl, and Green Lantern Versus Aliens.
He is credited, along with fellow illustrator Mike Zeck, of designing the black-and-white costume to which Spider-Man switched during the 1984 Secret Wars miniseries, and later wore for a time. According to the Spider-Man 1/2 special, the costume began as a design by Zeck that Leonardi embellished. The plot that developed as a result of Spider-Man's acquisition of the costume led to the creation of the Spider-Man villain known as Venom.