The Sepik (/ˈsɛpɪk/) is the longest river on the island of New Guinea, and the third largest in Oceania by discharge volume after the Fly and Mamberamo. The majority of the river flows through the Papua New Guinea (PNG) provinces of Sandaun (formerly West Sepik) and East Sepik, with a small section flowing through the Indonesian province of Papua.

The Sepik has a large catchment area, and landforms that include swamplands, tropical rainforests and mountains. Biologically, the river system is often said to be possibly the largest uncontaminated freshwater wetland system in the Asia-Pacific region. But, in fact, numerous fish and plant species have been introduced into the Sepik since the mid-20th century.

In 1884, Germany asserted control over the northeast quadrant of the island of New Guinea, which became part of the German colonial empire. The colony was initially managed by the Deutsche Neuguinea-Kompagnie or German New Guinea Company, a commercial enterprise that christened the territory Kaiser-Wilhelmsland. The first European ship to enter the Sepik estuary was the Samoa in May 1885. But the river, in fact, did not yet have a European name. It was thus termed Kaiserin Augustafluß by the explorer and scientist Otto Finsch, after the German Empress Augusta.

The word Sipik was first reported by A. Full as one of two names for the watercourse—the other being Abschima—used by the natives living at the mouth of the river. A few years later, Leonhard Schultze applied the term Sepik to the entire watercourse, and it took, although Schultze also noted another name for the river, Azimar. William Churchill, writing in the Bulletin of the American Geographical Society, said "These are not names of the river, they are but names for small stretches of the river as known to the folk of this or that hamlet. We cannot reckon how many such names there may be in the course of more than 600 miles [970 km] of the system." Since "there is no indigenous name for the whole stream", Churchill concluded that "This is clearly a case where a European designation may properly be applied." He advocated for Kaiserin-Augusta, but that name faded with the German loss of colonial control over the territory after World War I. The word Sepik henceforth became the official name of the river.

Of course, each language group had one or more names of its own for the river. For example, the Iatmul people call the river Avusett, a compound of "bone" (ava) and "lake" (tset).

The river originates in the Victor Emanuel Range in the central highlands of Papua New Guinea. From its mountain headwaters near Telefomin, it travels north-west and leaves the mountains abruptly near Yapsei. From there it flows into Indonesian Papua, before turning back north-east, for the majority of its journey following the great Central Depression. Along its course it receives numerous tributaries from the Bewani and Torricelli Mountains to the north and the Central Range to the south, including the Yuat River formed by the Lai and the Jimmi.

For most of the Sepik's length, the river winds in serpentine fashion, like the Amazon, to the Bismarck Sea off northern Papua New Guinea. Unlike many other large rivers, the Sepik has no delta whatsoever, but flows straight into the sea, about 100 km (62 mi) east of the town of Wewak. It is navigable for most of its length.

The river has a total length of over 1,100 km (680 mi) and has a drainage basin of over 80,000 km² (31,000 sq mi). Its meandering bed is 250–500 m (820–1,640 ft) wide and averages 8–14 m (26–46 ft) deep. There is a 5-to-10-kilometre-wide (3.1 to 6.2 mi) belt of active meanders along most of its course, that has created a floodplain up to 70 kilometres (43 mi) wide, with extensive backwater swamps. There are around 1,500 oxbow and other lakes in the floodplain, the largest of which are the Chambri Lakes. Its annual sediment load is estimated at 115 million tonnes.