The traditional definition of the region boundary can be traced back to early colonial districts in the British Province of Quebec and Upper Canada.

Indigenous peoples had occupied Eastern Ontario for thousands of years prior to European settlement.

Archaeological sites such as the Point Peninsula Complex indicate the presence of Paleo-Indians in the area dating back approximately 9,000 years.

Initial European settlement and colonization of the region occurred in the 17th and 18th centuries by the French and by fur traders as part of the colony of Canada within New France.

Further development of the community was spurred during the construction of the Rideau Canal, conceived as an alternate waterway bypassing the St. Lawrence River, a vulnerable location to American attacks following the War of 1812.

[6] The town was formally established as Ottawa in 1855, and remained inconsequential until it was selected as the permanent capital of Canada by Queen Victoria in 1857.

[9] The region's economy was initially focused largely on the fur trade, forestry, mining, and agriculture when the major cities were all colonial outposts.

[10] (2021)[11] (2016)[11] (2011)[11] (2006)[11] (2001)[11] (km2)[11] (km2)[12] density (/km2) Eastern Ontario is located within both the Mixedwood Plains Ecozone (as classified by Environment and Climate Change Canada, further subclassified into the St. Lawrence Lowland, Frontenac Axis, Manitoulin-Lake Simcoe regions),[14] and Boreal Shield Ecozone (further subclassified into the Algonquin-Lake Nipissing region).

[15] Surficial geology largely consists of glacial till, glaciolacustrine and glaciomarine silt/clay plains, and low-lying wetlands underlain by sedimentary limestone, dolostone, siltstone, sandstone, arkose, and shale bedrock, in addition to sections of plutonic igneous granite, quartz, gneiss, and conglomerate bedrock of the Canadian Shield, which is exposed at the surface in many locations.

More severe earthquakes (Richter Magnitude scale of 5-6 or greater) occur at a frequency of approximately 60 years on average.

Eastern Ontario maintains significant forest coverage, predominantly in the areas of the Canadian Shield that could not be cleared for agricultural purposes.

One major federally protected area, Thousand Islands National Park, is located in Eastern Ontario.

Eastern Ontario also regularly experiences severe weather events, including tornadoes, and thunderstorms as a result of humid summer temperatures.

The vast majority of the primary vehicular traffic network in Eastern Ontario is served mainly by the controlled-access 400-series highways.

Lawrence Seaway system, most major port activities are located upstream in Thunder Bay, Windsor, and Hamilton, or downstream in Montreal and Quebec City.

Other smaller locally-operated ferry services provide transit through the Thousand Islands on the Canadian side of the St. Lawrence River.

A bid for a Major League Soccer franchise was made by former Ottawa Senators owner Eugene Melnyk in 2010,[36] with intention of constructing a new stadium in Kanata.

[37] The Ottawa bid was ultimately rejected in favour of the Portland Timbers and Vancouver Whitecaps expansion teams.