Rising in the Acarai Mountains near the Brazil–Guyana border, the Essequibo flows to the north for 1,014 km (630 mi) through forest and savanna into the Atlantic Ocean.

[11] There are many rapids and waterfalls (e.g., Kaieteur Falls on the Potaro River) along the route of the Essequibo, and its 20-kilometre (12 mi) wide estuary is dotted with numerous small islands.

[17] During floods the headwaters of the Branco River (a part of the Amazon basin) and those of the Essequibo are connected, allowing a level of exchange in the aquatic fauna such as fish between the two systems.

In 1596 Lawrence Kemys, serving as second-in-command of Walter Raleigh's British expedition to Guiana, led a force inland along the banks of the Essequibo River, reaching what he wrongly believed to be Lake Parime.

[19] The Dutch colonists remained on friendly terms with the Native American peoples of the area, establishing riverside sugarcane and tobacco plantations.

A letter written by Venezuela's legal counsel, named partner Severo Mallet-Prevost of New York City law firm Curtis, Mallet-Prevost, Colt & Mosle alleged that the Russian and British judges on the tribunal had acted improperly and granted the lion's share of the disputed territory to Britain due to a political deal between Russia and the United Kingdom.

An estimated 4 million cubic metres (140,000,000 cu ft) of waste laced with cyanide was released into the river causing much destruction.

[23] As part of a British Technical Assistance project "Operation El Dorado", geologists Dr. Jevan P. Berrangé and Dr. Richard L. Johnson made the first topographic and geological maps of Guyana south of latitude 4 degrees north.

They examined 1:60,000 scale panchromatic aerial photos with a stereoscope to interpret the physical features and the geology of the region prior to making four expeditions into the field to check their observations.

The secondary purpose was to demonstrate the abilities of a new type of small hovercraft, the Cushioncraft CC7, thereby promoting sales of this British invention.

Fuel dumps for the hovercraft were laid down at intervals ahead of the expedition, by boat on the Rio Negro, by plane in the North Savannas and by float-plane on the Essequibo.

As there were no reliable maps of the route, navigation in Guyana was done by 1:60,000 scale aerial photographs and by scouting rapids in a motorised inflatable dinghy ahead of the CC7.

It was sponsored by the French-German TV Company ARTE and was organized by Duane De Freitas (Rupununi Trails) and the film production team of Marion Pöllmann and Rainer Bergomaz (Blue Paw Artists).

In 2018, with the support of the First Lady, Sandra Granger, a group consisting of five Wai-wai, two English, one Iranian, and one South African located the furthest source of the Essequibo River.

This team, accompanied later further downriver by Fay James (Macushi people), then paddled the remaining distance to the mouth of the Essequibo where it meets the Atlantic Ocean.

Team members: Laura Bingham (expedition leader), Ness Knight, Pip Stewart, Peiman Zekavat (film director), Jon Williams (cameraman), Nereus Chekema, Nigel Isaacs, Jackson (Elijah) Marawanaru, Aron Marawanaru, James Suse, Fay James, Romel Shoni, and Anthony Shushu.