Murphy began Toots and Casper in the New York American and other Hearst newspapers during December 1918. He used his wife, Matilda Katherine Murphy, as the model for Toots. The following year, the strip was picked up by King Features Syndicate in 1919, and the Sunday page began July 1920. The couple had a child, a boy named Buttercup, in November 1920. Buttercup remained a baby for over 20 years, eventually growing up as a six-year-old in the early 1940s.
Both the daily and the Sunday strips were popular favorites for decades. In 1934, Murphy included collectible stamp-like images in his Sunday strips, and these were so popular they were subsequently imitated by other cartoonists. There was a wave of Toots and Casper licensing and merchandising, with items that ran the gamut from dolls to comic books. Thelma Hill and Bud Duncan starred in the 1927-29 series of Toots and Casper silent comedy film shorts with Cullen Johnson as Buttercup and George Gray as Casper's boss.
The daily ran until 1951, and the Sunday strip continued until 1956. Murphy's illness near the end of the run prompted the recycling of earlier strips and the hiring of ghost artists.