Stapleford's origins can be traced to before Norman times. In the churchyard of St Helen's church is the Stone Cross which dates back to Saxon times and is said to be the oldest Christian memorial in the Midlands. Stapleford owed its development in part to its closeness to the River Trent and the River Erewash as the town became a central point for trade. The antiquary John Weever defined a staple town "to be a place, to which by the prince's authority and privilege wool, hides of beasts, wine, corn or grain, and other exotic or foreign merchandize are transferred, carried or conveyed to be sold." The area also expanded during the late 18th century when the stocking hose trade thrived in the Midlands. Evidence of this history can be found today with the original Stocking Knitters Houses still standing alongside more modern properties and shops such as on Nottingham Road. The main crossroads in Stapleford at the junction of Nottingham Road, Derby Road, Toton Lane and Church Street is called The Roach. The name is from the time when French prisoners from the Napoleonic Wars were set the task of cutting through rock to create roads and this was referred to as the 'La Roche'.
Stapleford is also home to the Hemlock Stone, which is situated on Stapleford Hill. It is approximately 200 million years old, dating back to the Triassic Period. Many theories surround why it exists.
During March 2006, a new NHS Health Centre and 'Walk-In Centre' was opened in the town (the Walk in Centre is now closed) A Sainsbury's local was opened on the site of the former Total petrol station in 2007. The town is often referred to informally as "Stabbo".
More recently it is the home of the Full Mash microbrewery, currently producing 5 BBL. The brewery regularly features in the Locale scheme.