In June 1842, Mary Smith arrives in Cranford to stay with her mother's friends Miss Matty and Miss Deborah Jenkyns. Cranford is a small town, on the edge of modernization. The railway now reaches Manchester and there is much change in the air. The village gossips are all aflutter when the local doctor announces that his cousin's son, Dr. Harrison, will soon be joining him in his medical practice. Harrison is a young bachelor who brings new medical ideas to the community. When the local tradesman, Jem Hearne, has an accident Harrison decides to try and save his arm rather than amputate it. Mary offers to assist him in the operation. Lady Ludlow plans her annual garden party and hopes that her long-absent and spendthrift son may return from Italy. The village welcomes other new residents when Captain Brown and his two daughters, one of whom is ill, move into the house across from the the Jenkyns'.

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After a few months in the village, Dr. Harrison has caught the eye of several of the young ladies. He has focused his attention on the parson's daughter, Sophie Hutton, and hopes to spend some time with her at Lady Ludlow's garden party. Her younger brother Walter takes ill however. Captain Brown receives a visit from Major Gordon who has an interest in his daughter, Jessie. While she too is interested in the Major, she's not sure she can leave her father alone. Mayhem ensues when Mrs. Forrester's cow, Bessie, goes missing after someone leaves the gate open. Lady Ludlow's estate manager Mr. Carter catches young Harry Gregson trespassing but decides to hire him rather than report him to the constable. Matilda meets someone from her past. Rumors have it that the railway may be coming to Cranford.

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It's Christmas-time and Miss Matty isn't sure it would appropriate to celebrate with friends and neighbors given the death of her sister. Mary Smith convinces her otherwise. Matty renews her friendship with her long ago love. Dr. Harrison hopes for a Christmas invitation from the Huttons but none is forthcoming as Sophy is uncomfortable in his presence since the death of her little brother. The residents of Cranford are suffering through a crime spree when Dr. Harrison's house is broken into and Mr. Johnson is attacked as he is closing his store. When Gregson is arrested for the crimes, young Harry has to admit that he and his father were out poaching at that time. By the time Valentine's day rolls around, Dr. Harrison's approach to Sophy receives a more positive reception. However, Miss Caroline Tomkinson receives an anonymous Valentine card and is more convinced than ever that Dr. Harrison is available.

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Railway construction begins. Dr. Harrison speaks to Sophy's father and he agrees that they can step out together. Harrison emphasizes that he cannot ask for her hand until he is better established and his practice more prosperous but that his intentions are entirely honorable. Caroline Tomkinson cannot understand why Dr. Harrison has not contacted her since receiving her Valentine day card so her sister decides to probe him. Mrs. Rose and her friends also misinterpret the Doctor's actions. Jessie Brown regrets having turned down Major Gordon's proposal of marriage and Mary Smith decides to do something about it. Lady Ludlow is not impressed when she learns that Mr. Carter has been teaching Harry Gregson to read and write and that he has been working in his office. Miss Matty's financial situation is severely affected when she learns that her bank has failed. May Day celebrations lead to confusion and confrontation when several ladies claim Dr. Harrison's affections.

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Martha and Jem are married and move into Miss Matty's home as lodgers. Dr. Harrison learns that Sophy has been sent away to stay with an aunt in Shropshire. When she returns home she contracts typhoid. Lady Ludlow mortgages the estate against Mr. Carter's advice. The ladies of Cranford decide they want to help their friend Miss Matty in her time of need. Mary manages to identify the man who sent the Valentine cards. Mr. Carter is injured in an explosion at the railway construction site and dictates his last will and testament. Major Gordon returns to Cranford but he also has a surprise for Miss Matty.

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