The Southern Tier is a geographic subregion of the broader upstate region of New York State, geographically situated along or very near the state border with Pennsylvania. Definitions of the region vary widely, but generally encompass counties surrounding the Binghamton, Elmira-Corning, and Jamestown metropolitan areas, along with the land of the Seneca Nation. This region is adjacent to the Northern Tier of Pennsylvania, and both these regions together are known as the Twin Tiers.

Geographically, most of the Southern Tier resides in the Allegheny Plateau of the Appalachian Mountains, with the eastern areas of the region nestled in the western portion of the Catskill Mountains. A longtime home of the Iroquois Confederacy, European settlers moved to the region after the American Revolutionary War. The fertile yet hilly land, combined with sweeping river valleys, led the region to support a combination of manufacturing industries (including large companies such as IBM and Corning Inc.) and farming, but with less development compared to neighboring subregions of upstate. Since the 1950s, the area is often considered to be a part of the Rust Belt, as manufacturing jobs have left the region.

As is the case with many regions in New York State, there is no legal definition of the Southern Tier, resulting a lack of consensus about which counties belong to the region. One of the broadest definitions of the Southern Tier is from the New York State Department of State, which classifies the following 14 counties as members of the Southern Tier:

This definition corresponds to the same 14 counties in New York State that are members of the Appalachian Regional Commission. Based on this definition, the Southern Tier partially overlaps with the Western New York, Finger Lakes, and Mohawk Valley regions. Less expansive definitions can vary widely, such as the eight-county region defined by the state's Empire State Development Corporation or the four-county region in the Encyclopedia of New York State.

Much of the Southern Tier is in area code 607, with the exception of Allegany, Cattaraugus, and Chautauqua Counties, which are in area code 716 or area code 585. As of 2023, the westernmost portion of the Southern Tier is located in New York's 23rd congressional district, and the easternmost portion is located in New York's 19th congressional district. The ZIP code prefixes 137 – 139 (Binghamton region), 147 (Jamestown region), and 148 – 149 (Elmira region) are set aside for the Southern Tier.

The Southern Tier is generally hilly without being mountainous (with the exception of the Catskill mountains). This can range from low rolling hills to more steep and rugged cliffs and valleys. The highest point in western New York is Alma Hill in Allegany County near the Steuben County line in the Southern Tier. Both the Delaware and Susquehanna rivers flow through the Southern Tier in their upper reaches, as does the Allegheny River in the western Southern Tier.

The Southern Tier makes up the northernmost portion of Appalachia and lies on the Allegheny Plateau. It is defined on its western boundary by the Chautauqua Ridge in Chautauqua County, and including this ridge and extending eastward across the northern bounds of the region, the continental divide between the Great Lakes and the Mississippi River watersheds exists. The Eastern Continental Divide runs directly through the region, in Steuben County.

The Southern Tier is more geographically linked with Pennsylvania and the Susquehanna River valley, at its confluence with the Chemung River, than it is with the remainder of New York State. Historically, the population of the Southern Tier came primarily from Pennsylvania, New Jersey, and downstate New York ("Yorkers"). In contrast, the inhabitants of upper New York State came from New England ("Yankees").