Common people started to settle in Ostrów Mazowiecka relatively late. At first, only a hunting manor owned by the Mazovian dukes and a trade settlement had existed at the site. In 1434, Mazovian Duke Bolesław IV chartered the local village, thus granting it the status of a town (under the name Ostrowia). The locality experienced rapid development, especially commercial development, in the 16th century, after Mazovia was incorporated into the Crown. Four fairs a year and one market a week were held in the town.

In the 17th century, Ostrów was one of the largest towns in eastern Mazovia and a renowned centre of trade and crafts. The town enjoyed the status of a municipal district. Unfortunately, the numerous wars taking place throughout the 17th century significantly weakened the economic position of the town and decimated its population. In 1795, Ostrów became part of the Prussian partition. In 1807, it was incorporated into the Duchy of Warsaw, and in 1815 – into the Kingdom of Poland. Many inhabitants of Ostrów participated in the January Uprising, which is why the region suffered painful repressions after the fall of the rebellion. The tsarist authorities sent two infantry and artillery regiments to station in the town. When it came to economy, however, the 19th century was a period of development of petty trade and transportation – the town gained a railway connection in 1893.

In 1926, the town was renamed to Ostrów Mazowiecka. In the interwar period, several industrial plants were opened in the town: brickyards, cement production plants, mills, an electricity plant. The industrial development of Ostrów was hampered by the outbreak of WWII. On 8 September 1939, Germans seized the town. Ca. 11,500 residents of the town died under the German occupation, most of them Jews. In the years 1941–1943, a Soviet POW camp was set up in the nearby localities of Grądy and Komorowo. Many inhabitants of the town were involved in the activities of the resistance movement. Ostrów became the seat of the “Opocznik” division of the Home Army. Ca. 60% of the town’s buildings and infrastructure was destroyed in warfare.

The postwar period saw the reconstruction of the town. New industrial plants were established, for example ZURAD and BUMAR, as well as a dairy and a furniture factory. A new hospital was also opened.