It's 1958 and Nurse Jenny Lee discovers the Nonnatus House community gathered to wish her a happy birthday as she returns from work. Chummy, Trixie and Cynthia then go to the cinema with her. Her good cheer is soon short lived though the next day when she is assigned a new patient called Molly Brignall. Trixie and Sister Evangelina end up in the middle of some unusual circumstances, aboard a Swedish cargo ship when they look after the captain's daughter, who is about to give birth for the first time.
The unexplained death of a newborn baby delivered by Cynthia puts the midwife under intense scrutiny from the police and the pregnant women of Poplar, placing immense strain on her work and health as she questions her own abilities. Chummy faces pressure of a different kind as she and PC Noakes pursue a dream which could bring exciting changes for the couple, while a chance encounter returns Jimmy to Jenny's life - with surprising results.
Jenny ends up being seconded to a short-staffed London Hospital to work on the male surgical ward and finds herself working under an intimidating surgeon, Mr Tracey. The midwives have a new addition called Jane, who lends a hand in Jenny's absence.
Jenny returns from her stint at the London Hospital and heads straight into one of the most emotive cases of her career when she and Sister Evangelina assist at the birth of a baby with spina bifida. As the parents struggle to come to terms with their son's life-limiting condition, Jenny, who has never delivered a disabled child, also fails to comprehend the far-reaching implications for the family. Meanwhile, Nonnatus House plays host to an acquaintance of Chummy - the Rev Applebee Thornton, an eccentric cleric who befriends Jane.
The whole Poplar community are getting ready for the annual Summer Fete. With the introduction of a Baby Show, the Nonnatus House midwives will be more involved than before. At the ante-natal clinic, Jenny meets Nora Harding, a mother of eight, who is upset that she may soon have another mouth to feed.
Crowded living conditions mean that tuberculosis has been rife in Poplar. A mass-Xray programme to diagnose the disease early though is introduced and Dr Turner is determined that the community will no longer live under the threat of the disease. The nuns and nurses attempt to support the doctor in his campaign to bring proper screening facilities to the area and Jenny's district nursing rounds lead her to a family who have suffered devastating misfortune from the disease.
Cynthia has to administer daily insulin injections to diabetic John Lacey, a bully who consistently belittles his wife Annie. When Annie's beloved son Bob pays a visit, Annie gains the confidence to start to turn her life around. Jenny looks after a black mother to be, Monique, who is subjected to racial prejudice from her neighbours.
The convent comes under threat as old buildings are been demolished to make room for new flats. Fred's pregnant daughter Dolly and her young son come and stay with him. Jenny is wooed by a new love interest, Alec, a friend and colleague of Jimmy's. Chummy and PC Noakes prepare for the arrival of their baby.
Christmas 1958 is not just about the opening of presents, but also attempting to heal some deep wounds. Jenny’s relationship with Alec continues to progress and Shelagh gets ready for her quiet wedding to Dr Turner. Nonnatus House is awoken by a banging on the door as the police pay a visit. An unexploded bomb has been uncovered and the whole area has to be evacuated.