Merrick was apparently normal until about the age of five, when he began showing signs of a strange disorder that caused abnormal growths of much of his skin and bone. The size of his head increased to 3 feet (almost 1 metre) in circumference, with spongy skin hanging from the back of his head and across his face; deformation of the jaws rendered him incapable of showing facial expression or speaking clearly. Although his left arm was normal, his right arm ended in a wrist that was 12 inches (30 cm) in circumference and a finlike hand. His legs were deformed in the same manner as his arm, and a defective hip caused such lameness that Merrick could walk only with the aid of a stick. The disorder from which Merrick suffered was long thought to be an extremely severe case of neurofibromatosis, but his deformities were probably the result of an extremely rare disease known as Proteus syndrome.

Merrick was confined to a workhouse at age 17, then escaped four years later to join a freak show (1883). While on exhibition, he was discovered by a London physician, Frederick Treves, and admitted to London Hospital (1886). He remained there until, at age 27, he died in his sleep of accidental suffocation.

A play about Merrick, The Elephant Man, by Bernard Pomerance, appeared in 1979; an unrelated motion picture based on Merrick's life was released in 1980.