Little is known about the natural history of this species. C. niobe has been recorded in the Democratic  Republic of Congo in montane tropical moist forest, secondary forest and adjacent to cultivated areas (Dieterlen and Heim de Balsac 1979). In Kibira National Park it is usually found in mesic habitats along shallow streams and sedge marshes, and in Mgahinga Gorilla National Park it was found within and near to sedge marshes (Bober and Kerbis Peterhans 2013). It is nocturnal and insectivorous (Bober and Kerbis Peterhans 2013).

Crocidura niobe occurs in montane forests in the Democratic Republic of the Congo, Uganda, Burundi, Rwanda and Tanzania. Mount Ruwenzori (1,890 m asl) in Uganda is the type locality for this species. In the Democratic Republic of the Congo it is found in the Kivu range, west of Lake Kivu (Dieterlen) and in the Mugaba Swamp and periphery forest and on the slope of Mt. Kahuzi (Kerbis Peterhans et al. 2010). In Burundi, specimens have been collected from the southern Bururi Forest Reserve at 2,170 m asl (Kerbis Peterhans et al. 2010) and in the north-west of the country from Kibira National Park between 1,950-2,250 m asl. In Uganda in addition to Mount Rwenzori C. niobe has been recorded in Bwindi Impenetrable Forest National Park at 1,600 m asl and in Mgahinga Gorilla National Park between 2,600-2,980 m asl (J. Kerbis Peterhans pers. comm.). It has been recorded in the Mahale Mountain National Park, Tanzania (J. Kerbis Peterhans, S. Ayebare & A.J Plumptre pers. comm. 2016). The species was found in Volcanoes National Park, Rwanda (Kerbis Peterhans and Austin 1996), but more recent surveys of the area failed to detect the species (Tuyisingize et al. 2013).

C. niobe is present in well-managed parks in Uganda, and is present in Kibira National Park in Burundi and Kahuzi-Biéga National Park in the Democratic Republic of the Congo. It has been recorded in the Mahale Mountain National Park, Tanzania (J. Kerbis Peterhans, S. Ayebare & A.J Plumptre pers. comm. 2016). Further details are needed on the natural history of this species, including its adaptability to habitat degradation.