The history of Baltimore spans back to 1659, when the Baltimore County was declared erected by the General Assembly of Maryland. The area where the city now lays was settled by David Jones in 1661. While this has been inhabited by Indigenous people since the 10th millennium BCE, it was not until European settlers arrived that it was given the name Baltimore, after the Province of Maryland's founding proprietor.

The city of Baltimore was founded in 1729. Early on, it was largely populated by German immigrants. The city gained prominence as a major hub for trade and commerce after successfully fending off British forces during the War of 1812. Seeing to maintain this position, the Baltimore & Ohio Railroad was established in 1829, making it one of the first commercial railroad lines in the world.

Before the Civil War, Baltimore was home to the largest free Black community in the U.S. It became known as a "city of refuge" and a destination for many former slaves, including Frederick Douglass. However, the city's growing Black population caused unease among white residents, leading to increased racial tensions after the war.

Baltimore has been the site of early organization for social movements, including women's suffrage and the civil rights movement of the 20th century.

The Baltimore area had been 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.

During the Late Woodland period, the archaeological culture known as the "Potomac Creek complex" resided in an area from Baltimore to the Rappahannock River in Virginia, primarily along the Potomac River downstream from the Fall Line.

In the early 17th century, the immediate Baltimore vicinity was populated by Native Americans. The Baltimore County area northward was used as hunting grounds by the Susquehannocks living in the lower Susquehanna River valley who "controlled all of the upper tributaries of the Chesapeake" but "refrained from much contact with Powhatan in the Potomac region." Pressured by the Susquehannocks, the Piscataway tribe of Algonquians stayed well south of the Baltimore area and inhabited primarily the north bank of the Potomac River in what is now Charles and southern Prince George's south of the Fall Line as depicted on John Smith's 1608 map which faithfully mapped settlements, mapped none in the Baltimore vicinity, while noting a dozen Patuxent River settlements that were under some degree of Piscataway suzerainty.

In 1608, Captain John Smith traveled 210 mi (340 km) from Jamestown to the uppermost Chesapeake Bay, leading the first European expedition to the Patapsco River, a word used by the Algonquin language natives who fished shellfish and hunted The name "Patapsco" is derived from pota-psk-ut, which translates to "backwater" or "tide covered with froth" in Algonquian dialect.