Battambang exists because of this water. The settlement began as a fishing village on the Sangkae in the eleventh century, and for most of its history the river, not any road, was the way in and out. Siam annexed the region in 1795 and ran it as the capital of Inner Cambodia; by 1880 the town held around 2,500 people and the Sangkae was its main link to Phnom Penh and Saigon. When the province was ceded to France in 1907 the colonial administration laid a grid of streets, cut open canals, and in 1917 threw two bridges across to tie the banks together - the layout that survives as Battambang's heritage conservation area today. A railway to Phnom Penh followed in 1926. The river has since been overtaken as a transport artery, but the city it produced is now Cambodia's third largest, and was named a UNESCO City of Gastronomy in 2023.

Five kilometres south of central Battambang, at Khwaeng pagoda, the river divides. The smaller fork swings east and passes through Sangkae village, six kilometres from the city centre, lending its name to Sangkae District. The main branch runs on into the Tonlé Sap floodplain about five kilometres below Preak Trob village, where it takes in the Serei Sophorn river at Prey Chas; the two branches find each other again at Thvang. From there the Sangkae stops behaving like a river at all. It spreads into the seasonally flooded forest of the western Tonlé Sap Biosphere Reserve and arrives at the lake near Prek Toal - a 42,000-hectare bird sanctuary declared a Ramsar wetland on 2 October 2015, and in the dry months one of the great waterbird gatherings of Southeast Asia. Whatever the Sangkae carries down from the mountains ends up here.

Along the banks, fishing is done with nets and with arrow-shaped traps set into the current, funnelling fish into a chamber they cannot reverse out of - a design that costs almost nothing and works without an engine. The river also gives villages their route to the lake's far richer fisheries. Upstream, the Sangkae system supplies drinking water and irrigation to roughly a million people before it ever reaches the Tonlé Sap. Because the whole system depends on fish that spawn in the flood, industrial fishing is closed during the wet-season peak from June to October. Human works have added their own complications. The Seksak hydropower plant sits on the river near Traeng, about 45 kilometres southwest of Battambang, and its dam has raised an artificial lake with a tourism resort on the shore - though by 2015 local people were arguing that the rising water was undermining the very attraction it created.

Industry has settled along the lower river, and the river has been sending back reports. In 2021 the provincial authorities opened an investigation into suspected chemical pollution after dead fish were found downstream. Two years later one company was fined 500,000 US dollars for dumping liquid waste into the Sangkae, and on 4 August 2023 the Provincial Administration announced a separate chemical leak from another plant. For a waterway that feeds drinking supplies, irrigated rice, a subsistence fishery and a Ramsar bird colony in a single 250-kilometre run, these are not local incidents. There is still a ferry that leaves Battambang and takes five or six hours to reach Siem Reap by way of the Sangkae and the open lake. It remains the best way to understand the river - not as a line on a map, but as the thing all of this is balanced on.