Jenny Lee gets ready to start her career as a midwife and is posted to Nonnatus House in London. She is surprised to find out that it is a nursing convent in the East End rather than a hospital. After managing to find her feet, she is given her first case, which is looking after a woman pregnant for the 25th time.
As Jenny Lee begins to settle into her role as there is a new arrival at Nonnatus House. The new girl Chummy attempts to show her worth but, with a keenness to please, and her inability to ride a bike, she finds it hard to earn the respect of Sister Evangelina. Jenny sees an unfamiliar darker side of life following an encounter with a runaway.
Jenny finds her name being put on the district nursing roster for a few weeks so that she can extend her experience of community practice. She looks after Joe, an old soldier with awful leg ulcers and begins to grow very fond of him. After his condition deteriorates, Jenny realises how much their friendship has changed her life. Trixie and Cynthia enrol Winnie Lawson as a new patient.
A baby girl who was recently delivered by Jenny ends up being snatched from her pram. The local community is united as they search for the missing child. Cynthia ends up seeing another sort of loss as she soon-to-be parents David and Margaret.
After Peggy's brother Frank is diagnosed with cancer, Jenny and the nuns are called upon to offer him the care that he needs. Jenny gets to know the siblings better. The other residents of Nonnatus House end up being involved in Fred's latest money-making scheme which involves a pig called Evie.
Sister Monica Joan is discovered walking around near the docks and returned to Nonnatus House by the local police. She ends up succumbing to pneumonia and after she gets better she herself in trouble with the policen she is accused of theft. All of her friends are worried that she could end up in jail. Chummy is owrried after her mother makes a trip to inspect her new 'beau'.
Christmas is just around the corner and the nuns and midwives of Nonnatus House are busier than usual. After an abandoned baby is found on the steps of the convent, the whole community comes together to offer food and clothing and attempt to locate his mother. Jenny Lee ends up getting caught up in a mystery that surrounds an elderly local woman called Mrs Jenkins. Chummy attempts to pull out all the stops to stage a memorable children's nativity play.