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 is returned to Nonnatus House by the local police. She ends up succumbing to pneumonia and after she gets better, she gets herself in trouble with the police when she is accused of theft, and all of her friends are worried that she could end up in jail. Chummy is worried 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.
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 Nonnatus community is left feeling stunned after the Kelly family's new-born son dies in some unexplained circumstances. Cynthia, who wat the the birth, comes under intense pressure from the police, and the pregnant women of Poplar. Chummy’s decision to pursue her dream brings about a different sort of pressure ro maried life as exciting changes lie ahead for the couple.
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 needs to use all her skills as a midwife as she and Sister Evangelina help at the birth of the Roberts’ baby, who is born with spina bifida. Nonnatus House plays host to an friend of Chummy’s, the Reverend Applebee Thornton, who is 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.
After the closure of Nonnatus House, the nuns and midwives finally move into their new premises. Sister Winifred arrives from the Mother House. Jenny is worried about new mother Merle’s mental state and the welfare of her baby who isn’t feeding properly. Dr Turner is worried that it could be something more serious.
Trixie is upset after Jenny is promoted, but the new Acting Sister has more important things to worry about after a mother-to-be reveals that the baby she is carrying is not her husbands and that the real father is black. Cynthia decides to give a lecture on natural childbirth, believing that it will help an overly anxious patient.
Sister Julienne gets a call from Holloway Prison where the Salvation Army, who normally offer midwifery for the inmates, have been struck down with influenza. She wants Trixie to help her at the prison and one of their patients called Stella, confesses that she’s scared that social services will think that she’s an unfit mother and take her baby away.
Jenny ends up having an eventful couple of days, beginning with trying to help a patient who is struggling to deal with her mother, an agoraphobic who hasn't been outside for at least 12 years. Alec wants Jenny to accompany her to Brighton for the weekend, leaving her wondering if his intentions are honourable.
Sister Julienne and Cynthia are getting donated clothing ready for charity. One parcel is set to go to St Gideon's, an institution which cares for those with disabilities and learning difficulties. Jacob, who suffers with cerebral palsy, helps Sally, who has Down’s syndrome, select a pretty cardigan to wear to the institution's annual dance. Following the dance, Sally’s mother discovers her feeling unwell and takes her to Nonnatus House to be looked at. The midwives find out that she is six months pregnant, which sees some difficult decisions needing to be made.
Tom and Fred are trying to spruce up an old bus outside of Nonnactus House which waylays the midwives who are due to set off on their rounds.
Cynthia is concerned that new mother Pamela is overly anxious, when Dr Turner arrives the mother and baby can't be found. Jenny returns and is seconded to The London were she soon begins to see cracks in the establishment. Chummy visits her mother in London. Tom cancels his first date with Trixie who tries to hide how she really feels about it.
Jenny pays a home visit to first time mother Jeanette and the two hit it off immediately, she is also introduced to Jeannette's cousin Philip. Chummy discovers her mother has discharged herself from hospital and her illness isn't getting any better. After a falling out, PC Noakes finding Lady Browne in great distress brings her to the home to be cared for in her final days.
Jennifer prepares for Christmas at home with Philip, and reminisces about her friends and colleagues back in her youth. Rehearsals get underway for the Sunday School Christmas concert, as Chummy tries to choreograph the dancing snowflakes. Chummy is also enlisted alongside Patsy to run a poorly managed mother and baby home. Cynthia is drawn into a case which concerns two former residents of a Victorian mental hospital who have been left to fend for themselves.