The 84-year old veteran will create characters for media including film, books, comics – and video games.
Lee's company, Pow! Entertainment, told the BBC that about 20 new characters, with names such as El Lobo, Chameleon, Thunder Rider, Whirlwind, Doubleman, Nightbird and Blaze, were already in the "active stages of development".
"I've got millions of them," Lee told the BBC. "I have filing cabinets filled with ideas for movies and television shows and all sorts of things.
"I've been waiting to be associated with someone like Disney so I can start tearing into these things."
Disney Studio chairman Dick Cook confirmed that the deal was designed to create characters and projects that could become franchises for Disney.