Born and educated in New York City, Byrnes was ten years old when he entered a contest that involved drawing a picture in a store window and won the prize, a $5 suit.

Byrnes planned a career in sports, but after he broke his leg during a wrestling match, he began copying the cartoons of Tad Dorgan while recuperating in the hospital.

Byrnes met Winsor McCay who gave him a letter of recommendation which led to work as a sports cartoonist.

In 1919, he began Wide Awake Willie as a New York Herald Sunday page, and this too featured Reg'lar Fellers characters.

[2] In 1923, he was interviewed by Helen Hilliard of The Oakland Tribune: I sat and watched Gene Byrnes draw a cartoon of himself for me.

This he dipped in India ink and with big swift strokes blotted out the penciled lines with streaks of heavy black.

there was the picture all finished, showing Gene Byrnes, cartoonist, with two Reg’lar Fellers on the top of his desk.

He overcame his limited drawing skills by hiring a phalanx of talented cartoonists to assist and ghost his strip, which continued to run in newspapers until 1948.