Having worked on nearly every major Marvel title throughout his prolific career, "Big John" Buscema had a great influence on the comic industry. His distinctive style and ability to flesh out characters visually helped bring a whole new generation of readers to the comic genre.

He had runs drawing company staples such as The Amazing Spider-Man, The Avengers, Daredevil, The Fantastic Four, and The Mighty Thor as well as classics like Tarzan, Doc Savage, and Howard The Duck. He also translated Marvin Wolfman's character concepts for The Man Called Nova into comic-book life by fully realizing Wolfman's rudimentary design for the character. The inker with whom he worked most often was Joseph Sinnott, who also worked for Marvel.

John Buscema began drawing comics in the 1950s and continued working for the next six decades, working with DC Comics for the first time in 2000. He died on January 10, 2002, at the age of 74, shortly after he had completed drawing the first issue of Justice League Of America: Barbarians. He had been diagnosed with stomach cancer a few months earlier.

In 2002 John Buscema was posthumously inducted into the Comic Book Hall of Fame.