Reverend Septimus Harding is much-loved in Barchester, perhaps the most beloved citizen in the county. In addition to the work at his church, which includes a superb choir, he is also Warden of a local hospital where a group of elderly gentlemen reside and receive a small stipend from the will of a benefactor who died some 400 years ago. Dr John Bold has been tasked to look into this will to determine if its wishes are being correctly applied. He is particularly concerned Harding is in receipt of an annual stipend of £800 per year — a considerable increase in the original amount owing to a vast increase in the value of the property — while its residents receive only 1s6d per day.

Eleanor pleads with Bold to stop his attacks on her father. He doesn't see his attack as personal but in fact against the perceived corruption of the Church of England, whose members live in luxury while the poor starve. In the end, he agrees to stop the court action and so informs Archdeacon Grantly, Harding's son-in-law. Eleanor and John agree to be married. It's not all that simple for Harding, however, as he's greatly disturbed by the accusations against him and travels to London to speak to the Church's solicitor, Sir Abraham Haphazard. Although the suit is dropped, he asks counsel if it's also a moral victory. When Haphazard says he's unable to speak to morality, Harding decides to resign as Warden.

Some years have now passed and Harding is happy in his new parish. Eleanor has wed John but he unexpectedly dies, leaving a widow with a young son. Bishop Grantly, well over 80 years old, also dies and his son, the Archdeadon, expects to be named Bishop in his place. Such is not to be, however, and the new Bishop and his wife soon arrive. Along with Bishop and Mrs Proudie comes his assistant Obadiah Slope. Archdeacon Grantly soon concludes that the new Bishop defers decisions to his wife and she to Slope. When the Bishop asks Slope to deliver the Sunday sermon at the Cathedral, Slope rails against the need for music during services, much to Harding's dismay. Slope is soon calling on the widowed Mrs Bold showing a great interest in her and suggesting that her father may be considered for his old post as Warden of the hospital.

As suggested by Proudie, Harding calls on Slope to discuss the possibility of being reappointed Warden of the hospital. Septimus is offended not only by Slope's manner but also the conditions he's laid down should the appointment be accepted. Slope is clearly using the appointment to his own advantage. Rather than arrange for a meeting with the Bishop as Septimus Harding had requested, he reports that Harding rejected the offer. Slope then offers the post to Mr Quiverful, who is more than pleased to accept, given that his household includes fourteen children. Slope continues to dangle the possibility of her father's appointment with Eleanor, in whom he has an interest — or at least interest in the fact that she is a rich widow.

Slope continues to manipulate those around him. Having overstepped the mark and offered the position of hospital Warden to Quiverful, he gets Proudie to agree that should Quiverful opt to withdraw his acceptance, they would be in a position to offer it once again to Harding. Slope manipulates the kindly Quiverful into withdrawing his acceptance but doesn't quite count on Mrs Quiverful, who goes straight to Mrs Proudie to complain. When the Bishop's wife learns that Slope used her name in his dealings with Quiverful, he makes an enemy that no man would dare want. Slope has also continued his visits to Signora Madeline Neroni, with whom he is clearly smitten. Meanwhile, Harding and Eleanor visit the Archdeacon and elder daughter Susan. Mr Grantly is still preparing to go to war with Slope and objects when Eleanor receives a letter from him.

Slope's machinations are slowly catching up to him. The Dean of Barchester Cathedral is on his death bed and many in the community are outraged when an article appears in the local newspaper suggesting that Slope should be named as his replacement. It's apparent to everyone that Slope was the source of the suggestion. At the Thornes' annual garden party, Eleanor is hoping to spend some time with Francis Arabin, whom she finds intriguing. Slope, however, seems to interrupt any such attempt and when he finally proposes to her, she has a very sharp – and painful – response. To her amazement, Slope's isn't the only marriage proposal she receives that day.

Mrs Proudie is in charge again and the Bishop announces that Quiverful is to become the new Warden of the hospital. Slope's objections fall on deaf ears as does his suggestion that he should be named Dean. He realises that his future is indeed dire. Harding is thrilled to be offered the post of Dean, leading his son-in-law and both daughters to rejoice. They're not prepared however for his response to the offer. Following Madeline Neroni's advice, Eleanor makes her feelings for Francis known.