A quadriplegic, Callahan draws his cartoons by clutching a pen between both hands. His visual artistic style is simplistic and often rough, although still legible. It has been likened to that of William Steig, James Thurber, Richard Condie, and Ben Wicks.
Callahan's cartoons deal with subjects often considered taboo. His black humor may be exemplified by the title of his "quasi-memoir", Will the Real John Callahan Please Stand Up?. The subject matter and treatment of his cartoons shares something with the work of Charles Addams and Gahan Wilson although it is much more aggressive than even the Playboy cartoons of these cartoonists.
Two animated cartoons have been based on Callahan's cartoons: Pelswick, a children's show on Nickelodeon; and Quads, a Canadian-Australian co-production, which retains the violence, joie de vivre and political incorrectness of his cartoons. The main character, who "walked out of a bar, and into a car" as the theme song relates, is a quadriplegic who won a large settlement from the rich driver who ran over him, and lives in a mansion with his buxom girlfriend, gay Australian physical therapist and a cast of fellow handicapees. Their outrageous adventures infuriate the neighbours which include an angry nun, the milquetoast millionaire who originally ran over the main character, and his domineering, Joan Riversesque wife.
Callahan's quadriplegia was caused by an automobile accident in 1972 at the age of 21. A proposed biographical movie, with Robin Williams in the title role, was in the planning stages in 2000 but was never produced.
John Callahan is currently working on a nudes and portrait project, shown in several galleries throughout its progression.
Callahan is also a songwriter. He released his first CD in 2006. The Independent of London calls his songs "Beautiful, but dark". He writes all the music and lyrics himself and is backed up by many notable musicians. A Dutch film crew recorded the studio sessions in which Callahan plays a simplified piano version of "Roll Away The Day". The album is produced by blues musician Terry Robb, with a special cameo appearance by Tom Waits.
John Callahan was adopted as an infant, and had five siblings. As a child, he was molested by a female teacher. He began drinking at the age of fourteen. “I used the alcohol to hide the pain of the abuse,” Callahan has said. After the car accident that caused his spinal cord injury, he went through extensive rehabilitation. At the age of 27, he gave up drinking alcohol. He lives in Portland, Oregon.
John Callahan's books include: