The Wisbech Museum Society was founded in 1835, initially occupying two rooms in a house at 16 Old Market Place. Admission in 1839 cost one shilling. The collections outgrew the space; in 1845 the building was sold; by 1847, a purpose-built museum had been constructed and opened. The opening lecture was delivered by Professor Adam Sedgwick, Vice-Master of Trinity College, Cambridge. The building, designed by architect George Buckler, cost between two and three thousand pounds, the capital raised through 100 shares of £25 each. It retains its original display cases and bookcases. Now Grade II* listed, it is recognized as one of the oldest purpose-built museums in the United Kingdom — older, in fact, than the Fitzwilliam Museum in Cambridge, a fact the museum notes with some satisfaction in its partnership with the University of Cambridge Museums.

The Wisbech and Fenland Museum's collections sprawl across time and geography with the organized enthusiasm of Victorian accumulation. Thomas Clarkson's chest — the one he carried through his decades of abolitionist campaigning, containing 18th-century African textiles, seeds, and leatherwork to argue for direct trade with Africa — is here. So is the Sèvres breakfast service reputedly belonging to Napoleon, said to have been captured at the Battle of Waterloo. A dismembered mummified hand is mounted on a red velvet cushion in the Egyptian collection. The Iron Age Wisbech Scabbard, dating to around 300 BC and found locally by Samuel Smith, is the jewel of the Celtic material. Hours of Idleness by Lord Byron and The Monk by Matthew Lewis sit in the manuscript collection alongside Dickens. The museum's natural history collection includes ichthyosaurs and shark teeth, Victorian bird and mammal mounts, and the early 19th-century botanical herbarium compiled by William Skrimshire.

The museum's local history collection tells the story of a particular landscape — the Fens — through the tools that shaped it and the industries that defined it. Agricultural implements, drainage equipment, and shooting and fishing gear trace the transformation of waterlogged marsh into one of England's most productive agricultural regions. The port of Wisbech, once described as England's most important for wheat export, is represented through shipping displays. Crime and punishment equipment — stocks, pillories, a gibbet — serve as reminders that the town's civic history was not always comfortable. A mantrap from Peckover House is on display. A model of a woad mill commemorates the Fenland dye industry. Bill posters for the Georgian Angles Theatre, one of England's oldest working theatres, fill a corner of the collection.

The museum building has a geological problem: it sits partly over the infilled moat of Wisbech Castle, and the settling of that fill has caused subsidence in the front elevation facing St Peter's Church. The museum was placed on the Heritage at Risk Register in 2018 before receiving a £616,000 grant from Historic England for roof repairs in 2021. Benjamin Zephaniah, visiting in 2018 to record a segment for the BBC2 series Inside Culture with Mary Beard, named the Wisbech and Fenland Museum his favourite museum in the country. The poet was onto something. It is a place where Dickens' manuscript and an Egyptian mummified hand and Thomas Clarkson's portable argument against slavery and a 2,300-year-old sword scabbard all coexist under a roof that needs occasional shoring up. It is, in the best sense, a very human place.