The midwives are based in Nonnatus House, which is named after St. Raymond Nonnatus (nonnatus being the Latin for "not born") who was born by Caesarean section, and is the patron saint of pregnant women and childbirth.

Long before Jennifer Worth's memoirs were filmed, she spotted Miranda Hart and knew that she would be perfect to play Camilla "Chummy" Fortescue-Cholmeley-Browne, the six-foot-one, ungainly, clumsy midwife who features in her books. Hart, who also hails from an aristocratic background like her character, agreed to take the role of Chummy if the books were ever filmed.

The newborns who appear on the show are a mix of at least four different prosthetic babies, including a tiny premature baby, a full-term baby, a mixed-race baby, and anatomically correct baby with interchangeable parts. However most shots are filmed with real babies who are around a week old.

Nonnatus House is a pseudonym for The Community of St. John the Divine, an Anglican religious order of nuns founded in London in 1848. The order relocated to Birmingham in 1976, and ceased to practice midwifery in 1990.

The series is based on the best-selling memoir of the same name by Jennifer Worth, the first in a trilogy of books describing her work as a district nurse and midwife in the East End of London during the 1950s. The premiere episode was dedicated to Worth's memory, as she died six months before it aired.

Stephen McGann, who plays Dr. Patrick Turner, is married to series writer Heidi Thomas.

Leonie Elliott, who joined the cast in series seven to portray Jamaican midwife Lucille Anderson, is also of Jamaican descent. Like Lucille, her family came to the UK in the 1960s. Her father's sister moved to the UK to train as a nurse like thousands of other women from the West Indies, and her mother's family came from Mandeville, the same parish from which Lucille originates.

Linda Bassett (Nurse Phyllis Crane) & Matilda Ziegler (Dulcie Roland) also worked together on Lark Rise to Candleford (2008) as Queenie Warner & Pearl Pratt respectively.

Pam Ferris plays another midwife in Children of Men (2006), looking after a pregnant girl.

Linda Bassett and Pam Ferris previously both worked on the mini-series Our Mutual Friend (1998).

Though their characters call off their engagement in the fourth series, Helen George (Trixie Franklin) and Jack Ashton (Rev. Tom Hereward) began an off-screen relationship in 2016 and welcomed a daughter in late 2017.