These states exploited the river's potential for navigation and commerce, operating a thriving trade in armor and weapons with neighboring countries, including Yamato period Japan.

Through the Silla, Goryeo, and Joseon periods, the river continued to serve as a major transportation corridor in the Gyeongsang region.

The southern length of the river formed the western portion of the Pusan Perimeter, which the UN forces fought to maintain during the autumn of 1950.

Despite being home to the bustling Port of Busan, the Nakdonggang estuary is internationally important for waterbirds, despite recent ecologically-destructive developments including reclamation for housing and industry (e.g. the Busan New Port), the ongoing construction of a major bridge (the Miyeonji Bridge) and most recently the threatened construction of the Korean Grand Canal project.

The Nakdonggang and its tributaries serve as a major source of drinking water for the inhabitants of the river basin and others nearby.

In the early 2010s, the Nakdonggang River was to be part of President Lee Myung-bak's canal project, the Grand Korean Waterway.

The project would link the Nakdong with the Han River to the north, creating a shipping canal spanning length of the country, from Seoul to Busan.

Encountering considerable controversy nationwide as well as from residents along the Nakdonggang, the waterway project was scrapped by the end of Lee's presidency.