The book covers the experiences of Ruby Lennox, a girl from a middle-class English family living in York. The museum of the title is York Castle Museum, which includes among its exhibits the facades of old houses from the city, similar to the one in which Ruby's family lives.
By interspersing flashbacks with the narrative of Ruby's own life, the book chronicles the lives of six generations of women from Ruby's great-grandmother Alice to Ruby's mother's failed dreams.
Ruby's own life is told in thirteen chapters, written in the first person, documenting key periods in Ruby's life from 1951 ( "Conception" beginning with the words "I exist!") to 1992. Between each chapter are (non-consecutive) flashbacks that tell the story from the point of view of one of the other members of Ruby's family—including her great-grandmother Alice, her grandmother Nell and her mother Bunty.
While mostly telling the story of the family's women, several of the flashbacks vividly depict the wartime experiences of their male relatives and lovers in both World Wars. One of the these depicts the crew of a Halifax bomber on a doomed last mission over Nazi Germany - which would become the main plot element in Atkinson's later "God in Ruins".