Newmarket's point on the Holland River long ago made the area a dominant portage route of travel between Lake Ontario and Lake Simcoe. In 1793, John Graves Simcoe travelled the trail. Choosing the eastern route as the better of the two, Simcoe started construction of Yonge Street along the old trail in late 1795, starting in York in Toronto Bay, and ending at the newly named St. Albans (Holland Landing), north of Newmarket.

In June, 1800, Timothy Rogers, a Quaker from Vermont, seek the area around the Holland River to find a suitable location for a new Quaker settlement. In 1801 Rogers returned along with several Quaker families who had left their houses in Vermont and Pennsylvania. By the Christmas of 1801, Joseph Hill had build up a mill on the Holland River, damming it to produce a mill pond that is now known as Fairy Lake. Hill also built a tannery just to the north of the mill, and the first store and house, as well as additional mills. By 1802, Elisha Beman had begun to base businesses and buy land in Newmarket. The town continued to grow through the early 19th century, along with the arrangement of Aurora and Holland Landing, and a market held in the current downtown location gave rise to the name "Newmarket".
Newmarket was integrated as a village in 1857 and in 1880 became a Town. In June 1853 the first train pulled into Newmarket on the Toronto, Simcoe & Lake Huron Union Railroad, the first railway in Upper Canada. It ultimately linked Toronto to Collingwood on Georgian Bay, a major shipbuilding centre. Today, this line is the "Newmarket Subdivision" of the Canadian National Railway system, functioning north out of Newmarket towards Bradford, and south towards Toronto.