The river's source is located in Mt. Kasadori in the Yamanashi prefecture. From there, it flows eastward into mountains of western Tokyo, where the Ogōchi Dam forms Lake Okutama. From there, it takes the name Tama, and flows eastwards through Chichibu Tama Kai National Park towards Ōme and then southeast between Tama Hills and Musashino Terrace. At Hamura is the source of the historic Tamagawa Waterway; built by the Tamagawa brothers in 1653 to supply water to Edo (present day Tokyo). Further downstream, the river forms the boundary between Tokyo and the city of Kawasaki in Kanagawa Prefecture. Its mouth on the heavily industrialised Tokyo Bay is next to Haneda Airport.
- The river flows through Tokyo, on the dividing line between Tokyo and Kanagawa. In the city, its banks are lined with parks and sports fields, making the river a popular picnic spot.