But when he realised Keaton didn't quite fit into Edward Scissorhands, he struck a friendship with this thespian wunderkind called Johnny. The rest is history, and a history we're glad about.
After the magnificent Edward came their masterpiece, about the worst filmmaker in the world: Ed Wood. This was followed by the creepy tale of Ichabod Crane, headless horseman: Sleepy Hollow.
And now comes Charlie And The Chocolate Factory, a dark reimagining of the Roald Dahl classic, which hits Indian theatres on Friday, September 9.
But this year will also see Corpse Bride, an eerily animated comedy where Depp naturally voices the leading man.
This relationship is the stuff of delicious nightmares, all light and cobwebs.
Text: Raja Sen | Design: Uday Kuckian