The name Portadown derives from the Irish name " Port an Dúnáin ", which means "Landing place (port) of the little fort". Little is known of the area prior to 1610 except that the area was sparsely populated by Irish Gaels. The dominant local clann was the Mac Cana (McCanns), known as the "Masters of Clann-Breasil" (Clanbrasil), who had been in the area since the 13th century. The Mac Cana were a sept of the Uí Néill (Ó Neills). The stronghold referred to in the Irish name Port an Dúnáin was likely the stronghold of the Mac Cana.

From 1594 until 1603, the Uí Néill and an alliance of other clanns fought a Nine Years' War against the English conquest of Ireland. This ended in defeat for the Irish clanns, and much of their land was seized by the English. In 1608, James I of England began the Plantation of Ulster - the organised colonization of this land by settlers from Great Britain.

In 1610, the lands of Portadown were granted to a William Powell. In 1611, he sold his grant of land to a Reverend Richard Rolleston, who in turn sold it in two portions to Richard Cope and Michael Obins. Michael Obins in conjunction with his mother, Prudence, secured a patent for a fair and market at Portadown in 1631, which led to the building of the first bridge across the River Bann shortly thereafter and there the history of the town really commences.

Obins built a large tower house and bawn (A bawn is the defensive wall surrounding an Irish tower house. It is the anglicised version of the Irish word badhún meaning "cattle-stronghold" or "cattle-enclosure".) and settled about twenty English tenants on the land around it (This was in the area of the present-day People's Park. Today this park is bounded on either side by Obins Street and Castle Street, both of which are reminders of "Obin's Castle"). During the Irish Rebellion of 1641, Obins Castle was captured by a force of dispossessed Irish led by the McCanns (Mac Cana), the Magennises (Mac Aonghusa) and the Ó Neills. The Irish Confederate troops abandoned the tower house during the Cromwellian conquest of Ireland, and Hamlet Obins (who had survived its capture) repossessed it in 1652. It was then passed to his son Anthony Obins.

In 1741, Anthony Obins was involved with the development of the Newry Canal. Around this time, Portadown became well known for the manufacture of cider. This indicated that there were already considerable plantings of apple trees in County Armagh. He was succeeded by Michael Obins in 1750.

In 1762 Michael Obins was given permission from the Irish House of Commons  to set up a linen market in Portadown. This linen market was in fact the foundation for the area's major industry. Obins and George Woodhouse established a general market in 1780. By the middle of the 19th century Portadown was exporting major quantities of grain, hay and straw to the other counties in Ulster as well as Scotland and England. 

Michael Obins died in 1798 and left a son, Michael Eyre Obins to succeed him. He resided in Castle Obins until 1814 and then took Holy Orders and settled in England. He sold his Portadown estates to the Sparrow family of Tandragee. A Miss Millicent Sparrow married Lord Mandeville in 1822, who later became the 6th Duke of Manchester. The Dukes of Manchester (Montague is the family name) thereafter were the landlords of Portadown as well as Tandragee.

This family's legacy to the town includes street names such as Obins Street, Castle Street, Montagu Street, Millicent Crescent and Mandeville Street, as well as buildings such as the Fergus Hall (formerly the Duke's School and Church Street PS), and the Carlton Home (the Duke's former townhouse, latterly a maternity hospital/nurses accommodation and now private apartments).