It flows through the Cariboo region of the British Columbia Interior, southeast of Prince George.

It flows generally west, picking up numerous tributary streams, many also draining ice fields.

After entering Bowron Lake Provincial Park, the Cariboo is joined by the Isaac River from the north, after which the Cariboo widens into Lanezi Lake, south of the Mowdish Range.

[5] At its western end Lanezi Lake empties into Sandy Lake, from which the Cariboo River flows first northwest, then abruptly south.

The Cariboo River flows south from Cariboo Lake, then turns west and empties into the Quesnel River at Quesnel Forks, northwest of Likely.