In 1940, the group made their feature-film debut, starring with Jack Benny in Love Thy Neighbor. One year later, they gained their own vehicle, San Antonio Rose, and backed Bing Crosby on his hit "Dolores" (from the film Las Vegas Nights). By that time, Cook had also left the group; her replacement, Marjory Garland, became a permanent member. The advent of America's involvement in World War II forced Joe into the service, while Lynn Allen served as his temporary replacement. The group's fifth film appearance, with Abbott & Costello in a Western called Ride 'Em Cowboy, influenced their material slightly, as versions of "Deep in the Heart of Texas" and "Jingle, Jangle, Jingle" became the Merry Macs' biggest hits yet.

A well-known version of "Praise the Lord and Pass the Ammunition" hit the Top Ten in 1942, and in 1944, the Merry Macs hit number one for the very first time. The nursery-rhyme novelty "Mairzy Doats" spent five weeks at number one during the year, and the group hit the Top Ten three additional times during the mid-'40s with "Pretty Kitty Blue Eyes," "Sentimental Journey," and "Laughing on the Outside (Crying on the Inside)." Joe McMichael died around this time, and he was replaced temporarily by Clive Erard and then by Dick Baldwin. Though the Merry Macs never charted after 1946, the group continued to tour and recorded for Capitol and Era Records before disbanding in 1964. A reunion concert followed in 1968, and various children of original group members have occasionally toured as the Merry Macs.