The province, in the Mekong River valley, is mostly plains. The northern part of the province has a more upland, forest-covered character. The main river in the northern part is the Songkhram River with the smaller Oun River. The southern part is flatter with the Kum River as its only notable watercourse. The provincial capital, the city of Nakhon Phanom, is on the banks of the Mekong.
Phu Lang Ka National Park covers 50 km² of forests and hills, and includes the Tat Kham and Tat Pho waterfalls as its most popular attractions. Flowers such as the Lady Slipper Orchid and diverse wildlife are found in the park.