In 1918, Tuthill launched Home Sweet Home, a strip about apartment life, in the New York Evening Mail. During the six-year run, it introduced George and Josephine Bungle, and he retitled it as The Bungle Family in 1924. Distributed initially by the McClure Syndicate and later by the McNaught Syndicate, the strip was carried by 120 newspapers. Comics historian Rick Marschall praised Tuthill's work, "Seldom has there been a strip (Moon Mullins comes to mind) registering a sustained, masterful indictment of petite-bourgeois sensibilities and preoccupations as did The Bungle Family."
He also drew Alice and Her Bothersome Little Brother and Napoleon Blunder during the 1920s. Little Brother ran as a topper strip to The Bungle Family. Tuthill’s strips from 1919 to 1926 were created in his home studio at 4537 Tower Grove Place in St. Louis, eventually moving to Ferguson, Missouri outside St. Louis. His sister, Irene Morrisson, also lived in the St. Louis area.
Tuthill continued to draw The Bungle Family for McNaught until he had a dispute with the syndicate in 1939, which no longer carried the strip in 1942. After a hiatus, the strip returned — syndicated by Tuthill himself — on May 16, 1943, with newspapers running a promotional banner, "The Bungles Are Back!" It ran for two more years until 1945 when Tuthill retired.