The series was a reflection of Danny Thomas' own life as an entertainer and the problems created by the frequent absences from his children. Even the title came from a phrase used in the real-life Thomas household: whenever Danny returned from a tour, his 2 daughters (Marlo and Terre) had to shift bedrooms to "Make Room For Daddy".

In the series, Danny plays nightclub entertainer Danny Williams, an occasionally loud and cantankerous, but ultimately warm and soft-hearted master of his domain. Constantly being upstaged by his bratty but loveable kids, played by Rusty Hamer, Angela Cartwright and Sherry Williams (whose role was taken over by Penny Parker), the ensemble also included beautiful Marjorie Lord as his understanding wife, and legendary character actor Hans Conreid as irascible Uncle Tonoose.

"Make Room For Daddy" was unique for many reasons, including how it portrayed the family life of an entertainer dealing with both industry and ordinary family issues. Another reason was its frequent appearances by top celebrities. In this Season 6 boxed-set, William Demarest, Jack Benny, Dinah Shore, Lucille Ball and Desi Arnaz, Tennessee Ernie Ford, Shirley Jones, and Bob Hope are but a few legendary performers lending their talents. In addition, upcoming stars had recurring roles, such as Tony Bennett as Danny's cousin Steven from Toledo, and Annette Funicello as Italian exchange student Gina Minelli.

"Make Room For Daddy" served as a springboard for then little known talents like Joey Bishop and Bill Dana, both of whom wound up with their own Danny Thomas produced television series. Other Thomas produced series include the Dick Van Dyke Show, Gomer Pyle, Real McCoys and Mod Squad.