St. Catharines is the most populous city in Canada's Niagara Region, the eighth largest urban area in the province of Ontario. As of 2021, St. Catharines has an area of 96.20 square kilometres (37.14 sq mi) and 136,803 residents. It lies in Southern Ontario, 51 kilometres (32 mi) south of Toronto across Lake Ontario, and is 19 kilometres (12 mi) inland from the international boundary with the United States along the Niagara River. It is the northern entrance of the Welland Canal. St. Catharines carries the official nickname "The Garden City" due to its 1,000 acres (4 km²) of parks, gardens, and trails.

St. Catharines is between the Greater Toronto and Hamilton Area (GTHA) and the Canada–U.S. border at Fort Erie. Manufacturing was the city's dominant industry, as noted by the heraldic motto, "Industry and Liberality". General Motors of Canada, Ltd., the Canadian subsidiary of General Motors, was the city's largest employer, a distinction now held by the District School Board of Niagara. THK Rhythm Automotive, formerly TRW, operates a plant in the city, although in recent years, employment there has shifted from heavy industry and manufacturing to services.

St. Catharines lies on one of the main telecommunications backbones between Canada and the United States, and as a result a number of call centres operate in the city. It is designated an Urban Growth Centre by the Growth Plan for the Greater Golden Horseshoe, intended to achieve a minimum density target of 150 jobs and residents combined per hectare by 2032 or earlier.

St. Catharines is also home to Brock University.

The Iroquoian speaking Chonnonton peoples who were also known as the "people of the deer" lived in the region. The Chonnonton would grow vegetables like corn, beans, and squash while living in longhouses. In 1647 the Seneca conquered Chonnonton villages from east of the Niagara River. The Haudenosaunee then destroyed the villages in the 1650s. After these attacks and smallpox epidemics, the Chonnontons disappeared completely, with the last recorded appearance of them in 1671 by French explorers.

St. Catharines falls within the original territory of the Mississaugas. A treaty signed in 1782 between the Mississaugas and the British government ceded a large tract of land, which included the St. Catharines area, to the Crown for the purpose of European settlement. St. Catharines was settled by Loyalists in the 1780s. The Crown granted land in compensation for services and for losses in the United States. Early histories credit the Loyalists Serjeant Jacob Dittrick and Private John Hainer as among the first settlers to come to the area in 1790. They took their Crown Patents, where Dick's Creek and 12 Mile Creek merge, which is now the city centre of St. Catharines. Historians have speculated that Dick's Creek was named after Richard Pierpoint, a Black Loyalist and former American slave, from an oral history account and events that had taken place around that time that would be consistent with him being the source of the name. Secondary to water routes, indigenous trails provided transportation networks, which resulted in the nearby radial road patterns. The surrounding land was surveyed, and ownships were created between 1787 and 1789.

After the Butler's Rangers disbanded in 1784 and settled the area, Duncan Murray, as a former quartermaster in the 84th Regiment of Foot (Royal Highland Emigrants), was appointed by the Crown to distribute free government supplies (victuals) for two years to the resettled Loyalists. He did this from his mill, built on the 12 Mile Creek in Power Glen. After his death in 1786, his holdings were forfeited to the merchant Robert Hamilton of Queenston, who tried to operate for profit the well-established Murray's Distribution Centre and Mill under the management of his cousin. Among other ventures, Hamilton became land wealthy by expropriating lands from subsistence Loyalist settlers who were incapable of settling their debts. Murray's distribution centre, later Hamilton's warehouse, and its location have long been a mystery. Hamilton's major profits were derived from transhipping supplies for the military and civic establishments from his Queenston enterprise, not from charitably supplying the subsistence Loyalist settlers. Hamilton lacked interest in social development and sold his business to Jesse Thompson before the turn of the 19th century.

The Merritt family arrived after this time and was among the later Loyalists to relocate after the American Revolution. They were from the Carolinas, New York, and New Brunswick. In 1796, Thomas Merritt arrived to build on his relationship with his former Commander and Queen's Ranger, John Graves Simcoe, who was now the Lieutenant Governor of Upper Canada. The first Welland Canal was constructed from 1824 to 1833. William Hamilton Merritt worked to promote the ambitious venture by raising funds and enlisting government support. The canal established St. Catharines as the hub of commerce and industry for the Niagara Peninsula. Merritt played a role in making St. Catharines a centre of abolitionist activity. In 1855, the British Methodist Episcopal Church, Salem Chapel; was established at the corner of Geneva and North Streets on land granted to the congregation by Merritt in the early 1840s. The area became known to refugee slaves from the United States as a place of "refuge and rest;" it was a destination, one of the final stops in Canada on the Underground Railroad for African-American refugees fleeing slavery. The abolitionist Harriet Tubman then lived in St. Catharines. By the mid-1850s, the town's population was about 6,000, of whom 800 were of African descent. St. Catharines remains an important place in Black Canadian history.