Madison is a city in and the county seat of Jefferson County, Indiana, United States, along the Ohio River. As of the 2020 census, Madison had a population of 12,357. Over 55,000 people live within 15 miles (24 km) of downtown Madison. Madison is the largest city along the Ohio River between Louisville and Cincinnati. In 2006, the majority of Madison's downtown area was designated a National Historic Landmark—133 blocks of the downtown area is known as the Madison Historic Landmark District.

Madison was laid out and platted in 1810, and the first lots were sold in 1811 by John Paul. It had busy early years due to heavy river traffic and its position as an entry point into the Indiana Territory along the historic Old Michigan Road. Madison's location across the Ohio River from Kentucky, a slave state, made it an important location on the Underground Railroad, which worked to free fugitive slaves. George DeBaptiste's barbershop in town became a nerve center of the local group. By 1850, Madison was the third-largest city in Indiana (after New Albany and Indianapolis), and among the 100 largest cities in the U.S.

Indiana's first railroad, the Madison & Indianapolis Railroad, was built there from 1836 to 1847. Chartered in 1832 by the Indiana State Legislature as the Madison Indianapolis & Lafayette Railroad, and construction begun September 16, 1836, the railroad was transferred to private ownership on January 31, 1843, as the Madison & Indianapolis Railroad. Successful for more than a decade, the railroad went into decline and was sold at foreclosure in 1862, renamed the Indianapolis & Madison Railroad, and after a series of corporate transfers, became part of the massive Pennsylvania Railroad system in 1921. In March 1924, the Madison Area Chamber of Commerce was founded to aid area business growth and development. Conrail much later bought Pennsylvania Railroad, but the deal left out a 26-mile (42 km) stretch of track from North Vernon to Madison. Madison Port Authority purchased this, forming Madison Railroad in 1975.

Madison's days as a leading Indiana city were numbered, however, when river traffic declined and new railroads built between Louisville, Indianapolis, and Cincinnati tapped into Madison's trade network. As a result, Madison's growth did not continue at the same pace it had experienced before the Civil War. During the late nineteenth century, many new buildings were still being built, but in many cases older structures were modernized by adding cast-iron storefronts and ornamental sheet metal cornices. Some earlier buildings survived without major alterations, and the Madison National Landmark Historic District today contains examples of all the major architectural styles of the nineteenth and early twentieth centuries, from Federal to Art Moderne.

In 1952 the town of North Madison was annexed, becoming a neighborhood of the city, which aided in providing city services to new businesses started in the area. A tornado in 1974 destroyed a number of buildings in the neighborhood.

On January 11, 1992, Shanda Sharer was murdered in the city by four teenage girls.

Downtown Madison was granted National Historic Landmark District status in early 2006. On August 25, 2006, just months after the designation, a blaze severely damaged two historic downtown buildings, the Madison Elks Lodge and a former city hall building that was occupied by an insurance company.

The Crawford-Whitehead-Ross House, Jefferson County Jail, Lanier Mansion, Madison Historic District, and Charles L. Shrewsbury House are listed on the National Register of Historic Places.