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.
Indiana State Road 7 has its southern terminus in Madison and leads northwest 23 miles (37 km) to Vernon.
Indiana State Road 56, the Ohio River Scenic Byway, is Madison's Main Street, leading east (upriver) 20 miles (32 km) to Vevay and west 23 miles (37 km) to Scottsburg.
According to the Köppen Climate Classification system, Madison has a humid subtropical climate, abbreviated "Cfa" on climate maps.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.Madison is one of the core cities of the Louisville-Elizabethtown-Madison metroplex, an area with a population of approximately 1.5 million. Route 421 passes through the center of town, crossing the Ohio into Kentucky on the Milton–Madison Bridge.In 2006, the majority of Madison's downtown area was designated the largest contiguous National Historic Landmark in the United States—133 blocks of the downtown area is known as the Madison Historic Landmark District. It is bordered to the south, across the river, by the city of Milton, Kentucky. US-421 leads north 26 miles (42 km) to Versailles, Indiana, and south 23 miles (37 km) to Campbellsburg, Kentucky.Shortly after an F-5 tornado struck Depauw, northwest of Louisville, the Hanover/Madison F4 twister formed near Henryville and traveled through Jefferson County, leveling many structures in the town of Hanover and in Madison.Eleven were killed in this storm, while an additional 300 were injured.The 1974 Super Outbreak is the second-largest tornado outbreak on record for a single 24-hour period.From April 3 to April 4, 1974, there were 148 tornadoes confirmed in 13 states, including Illinois, Indiana, Michigan, Ohio, Kentucky, Tennessee, Alabama, Mississippi, Georgia, North Carolina, Virginia, West Virginia, and New York; and the Canadian province of Ontario.Louisville is 48 miles (77 km) southwest of Madison by highway, and Cincinnati is 68 miles (109 km) to the northeast.Madison is bordered to the west by Clifty Falls State Park, encompassing the canyon of Big Clifty Creek and its tributaries, with several waterfalls, as well as high ground rising 400 feet (120 m) above the Ohio River valley.