Middlesbrough was incorporated as a municipal borough in 1853. It extended its boundaries in 1866 and 1887, and became a county borough under the Local Government Act 1888. A Middlesbrough Rural District was formed in 1894, covering a rural area to the south of the town. It was abolished in 1932, partly going to the county borough; but mostly going to the Stokesley Rural District.

Middlesbrough gained a "twin" in 1890 when the town of Middlesborough, Kentucky was incorporated in the United States; it was named after its English namesake due to the discovery of ironstone deposits in the region.

Middlesbrough is twinned with the German city of Oberhausen, Masvingo in Zimbabwe and Dunkerque ('Dunkirk' in English) in France. This latter association resulted from the Dunkirk evacuation of the British Expeditionary Force during World War II, in which one quarter of the ships involved were from Teesport.

In 686 a monastic cell was consecrated by St Cuthbert at the request of St Hilda Abbess of Whitby and in 1119 Robert Bruce granted and confirmed the church of St Hilda of Middleburg to Whitby. Up until its closure on the dissolution of the monasteries by Henry VIII in 1537, the church was maintained by 12 Benedictine monks, many of whom became vicars or rectors of various places in Cleveland. The importance of the early church at "Middleburg", later known as Middlesbrough Priory, is indicated by the fact that in 1452 it possessed four altars.

After the Angles the area became home to Viking settlers and it is argued by some that 'old' Cleveland has the highest density of Scandinavian parish names in Britain. Names of Viking origin are abundant in the area - for example, Thornaby, Ormesby, Stainsby, Lackenby, Maltby, Normanby, Tollesby, Ingleby (Barwick) and Lazenby which were once separate villages that belonged to Vikings called Thormad, Orm, Steinn, Hlakkande, Malti and Toll, but now form suburbs of Middlesbrough. Lazenby was the village belonging to a Leysingr - a freeman; Normanby, a Norseman's village and Danby (in neighbouring North Yorkshire), a Dane's village. The name Mydilsburgh is the earliest recorded form of Middlesbrough's name and dates to Anglian times (400 to 1000 A.D.), whilst many of the aforementioned villages appear in the Domesday Book of 1086.