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The river rises in the eastern Satpura Range of southern Madhya Pradesh state, and flows westward, draining Madhya Pradesh's Nimar region, Maharashtra's Kandesh and east Vidarbha regions in the northwest corner of the Deccan Plateau and South Gujarat before emptying into the Gulf of Cambay of the Arabian Sea, in the State of Gujarat.
The principal tributaries of the Tapti River are the Purna River, Girna River, Panzara River, Waghur River, Bori River and Aner River.
The river is dammed by Hatnur Dam in Jalgaon, Maharashtra.