Evidence of Stone Age, Roman, and Anglo-Saxon activity has been discovered locally. In the Middle Ages, Sale was a rural township, linked ecclesiastically with neighbouring Ashton upon Mersey, whose fields and meadows were used for crop and cattle farming. By the 17th century, Sale had a cottage industry manufacturing garthweb, the woven material from which horses' saddle girths were made.
The Bridgewater Canal reached the town in 1765, stimulating Sale's urbanisation. The arrival of the railway in 1849 triggered Sale's growth as a commuter town for Manchester, leading to an influx of middle class residents; by the end of the 19th century the town's population had more than tripled. Agriculture gradually declined as service industries boomed.
Sale's urban growth resulted in a merger with neighbouring Ashton upon Mersey, following the Local Government Act 1929. The increase in population led to the granting of a charter in 1935, giving Sale honorific borough status. Since then, Sale has continued to thrive as a commuter town, supported by its proximity to the M60 motorway and the Manchester Metrolink network. Sale Water Park contains an artificial lake used for water sports. Sale FC and Sale Sharks rugby union clubs and Sale Harriers athletics club were founded in Sale, although only the first now remains in the town at their Heywood Road ground.
A flint arrowhead discovered in Sale suggests a prehistoric human presence at the location, but there is no further evidence of activity in the area until the Roman period. A 4th-century hoard of 46 Roman coins was discovered in Ashton upon Mersey, one of four known hoards dating from that period discovered within the Mersey basin. Sale lies along the line of the Roman road which runs between the fortresses at Chester (Deva Victrix) and York (Eboracum), via the fort at Manchester (Mamucium); the present-day A56 follows the route of the road through the town. After the Roman departure from Britain in the early-5th century, Britain was invaded by the Anglo-Saxons.
Some local field and road names, and the name of Sale itself, are Anglo-Saxon in origin, which indicates the town was founded in the 7th or 8th centuries. The Old English salh, from which "Sale" is derived, means "at the sallow tree", and Ashton upon Mersey means "village or farm near the ash trees". Although the townships of Sale and Ashton upon Mersey were not mentioned in the Domesday Book of 1086, that may be because only a partial survey was taken. The first recorded occurrences of Sale and Ashton upon Mersey are in 1199–1216 and 1260 respectively. The settlements were referred to as townships rather than manors, which suggests further evidence of Anglo-Saxon origins as townships were developed by the Saxons.