Baltimore is the most populous city in the U.S. state of Maryland. It is the 30th-most populous U.S. city with a population of 585,708 at the 2020 census and estimated at 568,271 in 2024, while the Baltimore metropolitan area at 2.86 million residents is the 22nd-largest metropolitan area in the nation. The city is also part of the Washington–Baltimore combined statistical area, which had a population of 9.97 million in 2020. Baltimore was designated as an independent city by the Constitution of Maryland in 1851. Though not located under the jurisdiction of any county in the state, it forms part of the Central Maryland region together with the surrounding county that shares its name.

The land that is present-day Baltimore was once used as hunting ground by Paleo-Indians. In the early 1600s, the Susquehannock began to hunt there. People from the Province of Maryland established the Port of Baltimore in 1706 to support the tobacco trade with Europe and established the Town of Baltimore in 1729. During the American Revolutionary War, the Second Continental Congress briefly moved its deliberations to the Henry Fite House from December 1776 to February 1777 prior to the capture of Philadelphia to British troops, which permitted Baltimore to serve briefly as the nation's capital before it returned to Philadelphia. The Battle of Baltimore was pivotal during the War of 1812, culminating in the British bombardment of Fort McHenry, during which Francis Scott Key wrote a poem that became "The Star-Spangled Banner" and was designated as the national anthem in 1931. During the Pratt Street Riot of 1861, the city was the site of some of the earliest violence associated with the American Civil War.

The Baltimore and Ohio Railroad, the nation's oldest, was built in 1830 and cemented Baltimore's status as a transportation hub, giving producers in the Midwest and Appalachia access to the city's port. Baltimore's Inner Harbor was the second-leading port of entry for immigrants to the U.S. and a major manufacturing center. After a decline in heavy industry and restructuring of the rail industry, Baltimore has shifted to a service-oriented economy. Johns Hopkins Hospital and University are now the top employers. Baltimore is also home to the Baltimore Orioles of Major League Baseball and the Baltimore Ravens of the National Football League. It is ranked as a Gamma−world city by the Globalization and World Cities Research Network.

The city is home to some of the earliest National Register Historic Districts in the nation, including Fell's Point, Federal Hill, and Mount Vernon. Baltimore has more public statues and monuments per capita than any other city in the U.S. Nearly one third of the buildings (over 65,000) are designated as historic in the National Register, more than any other U.S. city. Baltimore has 66 National Register Historic Districts and 33 local historic districts.

The city is named after Cecil Calvert, 2nd Baron Baltimore, an English politician and lawyer who was a founding proprietor of the Province of Maryland. The Calverts took the title Barons Baltimore from Baltimore Manor, an estate they were granted by the Crown in County Longford as part of the plantations of Ireland. Baltimore is an anglicization of Baile an Tí Mhóir, meaning "town of the big house" in Irish.

The Baltimore area was inhabited by Native Americans since at least the 10th millennium BC, when Paleo-Indians first settled in the region. One Paleo-Indian site and several Archaic period and Woodland period archaeological sites have been identified in Baltimore, including four from the Late Woodland period. In December 2021, several Woodland period Native American artifacts were found in Herring Run Park in northeast Baltimore, dating 5,000 to 9,000 years ago. The finding followed a period of dormancy in Baltimore City archaeological findings which had persisted since the 1980s. During the Late Woodland period, the archaeological culture known as the Potomac Creek complex resided in the area from Baltimore south to the Rappahannock River in present-day Virginia.

In the early 1600s, the immediate Baltimore vicinity was sparsely populated, if at all, by Native Americans. The Baltimore County area northward was used as hunting grounds by the Susquehannock living in the lower Susquehanna River valley. This Iroquoian-speaking people "controlled all of the upper tributaries of the Chesapeake" but "refrained from much contact with Powhatan in the Potomac region" and south into Virginia. Pressured by the Susquehannock, the Piscataway tribe, an Algonquian-speaking people, stayed well south of the Baltimore area and inhabited primarily the north bank of the Potomac River in what are now Charles and southern Prince George's counties in the coastal areas south of the Fall Line.

European colonization of Maryland began in earnest with the arrival of the merchant ship The Ark carrying 140 colonists at St. Clement's Island in the Potomac River on March 25, 1634. Europeans then began to settle the area further north, in what is now Baltimore County. Since Maryland was a colony, Baltimore's streets were named to show loyalty to the mother country, e.g. King, Queen, King George and Caroline streets. The original county seat, known today as Old Baltimore, was located on Bush River within the present-day Aberdeen Proving Ground. The colonists engaged in sporadic warfare with the Susquehannock, whose numbers dwindled primarily from new infectious diseases, such as smallpox, endemic among the Europeans. In 1661 David Jones claimed the area known today as Jonestown on the east bank of the Jones Falls stream.