The Seti rises from the base of the Annapurna massif, and flows south and south-east past Pokhara and Damauli to join the Trishuli River near Devghat.

The river is also famous because of its proximity to some holy places and is the central point of many stories of Hindu mythology, such as the Mahabharata, one of the longest books of Hinduism, written by Vyasa, who was born near the confluence of the Gandaki and Madi rivers near Damauli, Tanahun, Nepal.

[2] The Seti Gandaki was successfully descended for the first time in June 1971 by Daniel C. Taylor and Jennifer Ide.

[3] A slurry of sediment, rock, and water suddenly surged through Pokhara Valley on May 5, 2012, obliterating dozens of homes and sweeping 72 people to their death.

On 15 January 2023, Yeti Airlines Flight 691 crashed on the Seti bank during approach to Pokhara International Airport, killing all 72 people on board.