In 1912, Webster drew a daily panel for the New-York Tribune, under a variety of titles—Our Boyhood Ambitions, Life's Darkest Moment, The Unseen Audience. In 1924, Webster moved to the New York World and soon after added The Timid Soul featuring the wimpy Caspar Milquetoast. Milquetoast developed out of the design of another character, Egbert Smear, or The Man in the Brown Derby. The character was said to have ushered in a new era of timidity in comics.
In 1927, Webster trained himself to draw left-handed in three months after a severe case of arthritis impaired the use of his right hand. In 1931, the World folded, and that same year, Simon & Schuster published a collection of The Timid Soul reprints. Webster then went back to the Tribune (now known as the New York Herald Tribune), where he launched a Timid Soul Sunday strip. He alternated his various features throughout the week: Caspar Milquetoast was seen on both Sunday and Monday. The character was featured in books, film, radio programs and vaudeville acts. Webster continued to produce this syndicated panel until his death in 1952, after which his assistant Herb Roth carried it on for another year.