The origin of the name Stretford is "street" on a ford across the River Mersey. The principal road through Stretford, the A56 Chester Road, follows the line of the old Roman road from Deva Victrix (Chester) to Mamucium (Manchester), crossing the Mersey into Stretford at Crossford Bridge, built at the location of the ancient ford.

The earliest evidence of human occupation around Stretford comes from Neolithic stone axes found in the area, dating from about 2000 BC. Stretford was part of the land occupied by the Celtic Brigantes tribe before and during the Roman occupation, and lay on their border with the Cornovii on the southern side of the Mersey. By 1212, there were two manors in the area now called Stretford. The land in the south, close to the River Mersey, was held by Hamon de Mascy, while the land in the north, closer to the River Irwell, was held by Henry de Trafford. In about 1250, a later Hamon de Mascy gave the Stretford manor to his daughter, Margery. She in turn, in about 1260, granted Stretford to Richard de Trafford at a rent of one penny. The de Mascy family shortly afterwards released all rights to their lands in Stretford to Henry de Trafford, the Trafford family thus acquiring the whole of Stretford, after which the two manors descended together.

Until the 1820s, one of the main cottage industries in Stretford was the hand-weaving of cotton. There were reported at one time to have been 302 handlooms operating in Stretford, providing employment for 780 workers, but by 1826 only four were still being used, as the mechanised cotton mills of nearby Manchester replaced handlooms. As Manchester continued to grow, it offered a good and easily accessible market for Stretford's agricultural products, in particular rhubarb, once known locally as Stretford beef. By 1836, market gardening had become so extensive around Stretford that one writer described it as the "garden of Lancashire". In 1845, over 508 tons of vegetables were being produced each week for the Manchester market. Stretford also became well-known for its pig market and the production of black puddings, leading to it being given the nickname Porkhampton.

Situated on the border with Manchester, Stretford became a fashionable place to live during the middle of the 19th century. Large open spaces were established, such as the Royal Botanical Gardens, opened in 1831. The gardens were sited in Old Trafford on the advice of scientist John Dalton, because the prevailing south-westerly wind kept the area clear of the city's airborne pollution. In 1857, the gardens hosted the Art Treasures Exhibition, the largest art exhibition ever held in the United Kingdom. A purpose-built iron and glass building was constructed at a cost of £38,000 to house the 16,000 exhibits. The gardens were also chosen as a site for the Royal Jubilee Exhibition of 1887, celebrating Queen Victoria's 50-year reign. The exhibition ran for more than six months and was attended by more than 4.75 million visitors. The gardens were converted into an entertainment resort in 1907, and hosted the first speedway meeting in Greater Manchester on 16 June 1928. There was also greyhound racing from 1930, and an athletics track. The complex was demolished in the late 1980s, and all that remains is the entrance gates, close to what is now the White City Retail Park. The gates were designated a Grade II listed structure in 1987.

The arrival of the Manchester Ship Canal in 1894 and the subsequent development of the Trafford Park industrial estate in the north of the town – the first planned industrial estate in the world – had a substantial effect on the growth of Stretford. The population in 1891 was 21,751, but by 1901 it had increased by 40% to 30,436 as people were drawn to the town by the promise of work in the new industries at Trafford Park.

During the Second World War, Trafford Park was largely turned over to the production of war material, including the Avro Manchester heavy bomber, and the Rolls-Royce Merlin engines used to power both the Spitfire and the Lancaster. That resulted in Stretford being the target for heavy bombing, particularly during the Manchester Blitz of 1940. Among the buildings damaged or destroyed during the war were Manchester United's Old Trafford football ground, All Saints' Church, St Hilda's Church, and the children's library in King Street. A memorial to those residents who lost their lives in the bombing was erected in Stretford Cemetery in 1948.

Between 1972 and 1975, what is now the B&Q store in Great Stone Road was the 3,000-capacity Hardrock Theatre and Village Discothèque, hosting some of that period's major artists in their prime. Led Zeppelin, David Bowie, Bob Marley, Elton John, Hawkwind, Yes, Chaka Khan, Curved Air and Lou Reed were amongst those who appeared. Tangerine Dream was the last band to perform at the Hardrock, on 19 October 1975.

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