The minor district (King Amphoe) was created on December 15, 1975, when the five tambon Senangkhanikhom, Rai Si Suk, Phon Thong, Nong Hai and Na Wiang were split off from Amnat Charoen district. It was upgraded to a full district on April 1, 1983. In 1993 it was one of the district split off from Ubon Ratchathani to form the new province Amnat Charoen.
The district is subdivided into 6 subdistricts (tambon), which are further subdivided into 58 villages (muban). Senangkhanikhom is a township (thesaban tambon) which covers parts of the tambon Senangkhanikhom. There are further 6 Tambon administrative organizations (TAO).