The Orinoco is by far the most important of the more than 1,000 rivers in the country. Flowing more than 2,500 kilometers to the Atlantic from its source in the Guiana highlands at the Brazilian border, the Orinoco is the world's eighth largest river and the largest in South America after the Amazon. Its flow varies substantially by season, with the high water level in August exceeding by as much as thirteen meters the low levels of March and April. During low water periods, the river experiences high and low tides for more than 100 kilometers upstream from Ciudad Guayana.

For most of the Orinoco's course, the gradient is slight. Downstream from its headwaters, it splits into two; one-third of its flow passes through the Brazo Casiquiare (Casiquiare Channel) into a tributary of the Amazon, and the remainder passes into the main Orinoco channel. This passageway allows vessels with shallow drafts to navigate from the lower Orinoco to the Amazon River system after unloading and reloading on either side of two falls on the Orinoco along the Colombian border.

Most of the rivers rising in the northern mountains flow southeastward to the Río Apure, a tributary of the Orinoco. From its headwater, the Apure crosses the llanos in a generally eastward direction. Few rivers flow into it from the poorly drained region south of the river and much of this area near the Colombian border is swampland.

The other major Venezuelan river is the fast-flowing Caroní, which originates in the Guiana highlands and flows northward into the Orinoco upstream from Ciudad Guyana. The Caroní is capable of producing as much hydroelectric power as any river in Latin America and has contributed significantly to the nation's electric power production. Electricity generated by the Caroní was one of the factors encouraging industrialization of the northern part of the Guiana highlands and the lower Orinoco valley.

The Lago de Maracaibo, the largest lake in Latin America, occupies the central 13,500 square kilometers of the Maracaibo lowlands. The low swampy shores of the lake and areas beneath the lake itself hold most of Venezuela's rich petroleum deposits. The lake is shallow, with an average depth of ten meters, and separated from the Caribbean by a series of islands and sandbars. In 1955 a 7.5-meter channel was cut through the sandbars to facilitate shipping between the lake and the Caribbean. The channel also allows salt water to mix with the yellowish fresh water of the lake, making the northern parts brackish and unsuited for drinking or irrigation.