Madison County is a county located in the U.S. state of New York. As of the 2020 census, the population was 68,016. Its county seat is Wampsville. The county is named after James Madison, the fourth president of the United States, and was first formed in 1806. The county is part of the Central New York region of the state.

Madison County is part of the Syracuse metropolitan area, and is home to both the International Boxing Hall of Fame and the National Abolition Hall of Fame and Museum.

Indigenous peoples had occupied areas around Oneida Lake for thousands of years. The historic Oneida Indian Nation is an Iroquoian-speaking people who emerged as a culture in this area about the fourteenth century and dominated the territory. They are one of the Five Nations who originally comprised the Iroquois Confederacy or Haudenosaunee.

English colonists established counties in eastern present-day New York State in 1683; at the time, the territory of the present Madison County was considered part of Albany County, with the city of Albany located on the Hudson River. This was an enormous county, including the northern part of New York State around Albany as well as all of the present State of Vermont and, in theory, extending westward to the Pacific Ocean. It was claimed by the English but largely occupied by the Oneida, Onondaga, Seneca, Cayuga and Mohawk, who had the territory in the central Mohawk Valley, as well as Mahican near the Hudson River. On July 3, 1766, the English organized Cumberland County, and on March 16, 1770, they organized Gloucester County, both containing territory now included in the state of Vermont.

On March 12, 1772, what was left of Albany County was split into three parts, one remaining under the name Albany County. One of the other pieces, Tryon County, contained the western portion (and thus, since no western boundary was specified, theoretically still extended west to the Pacific). The eastern boundary of Tryon County was approximately five miles west of the present city of Schenectady, and the county included the western part of the Adirondack Mountains and the area west of the West Branch of the Delaware River. The area then designated as Tryon County includes 37 current counties of New York State. The county was named for William Tryon, the colonial governor of New York.

In the years prior to the outbreak of revolution in 1776, tensions rose in the frontier areas upstate and most of the Loyalists in Tryon County fled to Canada. In 1784, following the peace treaty that ended the American Revolutionary War, New York changed the name of Tryon County to Montgomery County, in honor of the general, Richard Montgomery, who had captured several places in Canada and died attempting to capture the city of Quebec.

As allies of the Patriots, the Oneida Indian Nation was allocated land by the United States in the postwar settlement for a reservation near Oneida Lake, in their traditional homeland. In the postwar treaty, the four Iroquois nations who had been allies of the British were forced to cede their lands; most of their peoples had already migrated to Canada to escape the worst of the fighting on the frontier after Sullivan's Raid. This expedition through Indian country had destroyed dwellings, crops and winter stores; many Iroquois who did not migrate died of starvation that winter.

But settlers were hungry for land, and in 1788 Governor Clinton's representatives persuaded the Oneida to cede some of their territory to the state for sale to European-American settlers. This was called the "Clinton Purchase", after Governor George Clinton. The land comprised the southern portion of the Oneida reservation. It has also been called the Twenty Townships, as these were the number organized after New York controlled the land.