Eastern Canada's longest river,[2] its drainage basin is one of the largest on the east coast[3] at about 55,000 square kilometres (21,000 sq mi).

This “River of the Good Wave” and its tributary drainage basin formed the territorial countries of the Wolastoqiyik and Passamaquoddy First Nations (named Wolastokuk and Peskotomuhkatik, respectively) prior to European colonization, and it remains a cultural centre of the Wabanaki Confederacy to this day.

The lower basin, 140 kilometres (90 miles) to Saint John Harbour on the Bay of Fundy, consisting of lakes, islands, wetlands and a tidal estuary.

In the lower sections in the broader floodplain, flooding may occur during late spring from the volume of water which must make its way through the narrow gorge at the Reversing Falls.

Surface runoff from heavy rainfall is the main cause of flooding, and can be exacerbated by ice jams, high tides, and rapid snowmelt.

[19] At the end of the last glacial period, following the retreat of the Laurentide Ice Sheet about 13,000 years ago, the area was stripped bare of vegetation and soil.

[21] The Passamaquoddy hunted sea mammals along the northwest shore of the Bay of Fundy while speaking a mutually intelligible dialect with the Wolastoqiyik who were inland hunters along the upper Saint John River and its tributaries.

[21][11] Archaeological evidence is that the Wolastoqiyik had economic and cultural ties with large portions of North America[24] from their country's homebase within the Dawnland.

Early 16th century fur trade with French fishermen encouraged increased interest in the smaller tributaries and headwaters where scarcity of edible prey kept population density low.

[25] After spending the winter hunting and trapping in the interior, the villages of Ouigoudi at the mouth of the river and Aukpaque at the head of navigation were summer gathering places accessible to European fur traders.

[25] Ouigoudi was defensively fortified as Fort La Tour and Aukpaque became known as Sainte-Anne des Pays-Bas when Acadian colonists settled the lower river valley.

[27] The earliest Acadians were descendants of the French sailors and shipwrights whose focus on fishing, trading, and boat repair rather than agriculture minimized land use conflicts.

[28] These Acadians maintained favorable relationships with the First Nations while King Philip's War encouraged the Wolastoqiyik to join the Wabanaki Confederacy in military action against New England.

Canada chose to interpret the treaty's intention as keeping the entire Saint John drainage basin under Canadian control.

[33] Large numbers of people began settling the area in the early 1800s, mostly Scottish and Irish, and by the end of the 1850s much of the central Saint John valley had been cleared of old-growth forest for farming.

After the state of Maine obtained independence from Massachusetts in 1820, Maine lumbermen encouraged Acadian refugees to form the independent Republic of Madawaska,[34] and began diverting the Saint John headwaters into the Penobscot River so log driving could float timber harvested in the upper Saint John watershed to Bangor sawmills.

[36] Today's Trans-Canada Highway follows the route of the proposed English road along the north bank of the river through the disputed portion of the drainage.

Most of the Saint John drainage on the disputed south bank became Aroostook County, Maine, where the town of Madawaska still shares the Acadian French dialect with Edmundston across the river.

Spring snowmelt causes scouring ice jams along the upper river leaving bedrock covered by thin, patchy acidic soil supporting one of the highest concentrations of rare plants in Maine including Clinton's bulrush, Dry Land Sedge, Mistassini primrose, Nantucket shadbush, Northern Painted Cup, and Swamp Birch.