This species occurs with M. natalensis and M. erythroleucus in the same region. Karyotype of M. awashensis (2n = 32, FNa = 54, Lavrenchenko et al., 1998a; or 2n = 32, FNa = 52, Volobouev et al., 2002b) is dissimilar to that of M. erythroleucus (2n = 38, FN = 50) and resembles karyotype of M. natalensis from the Ethiopian Rift Valley (2n = 32, FNa = 54-56), but the two are distinguished by frequency of metacentric and submetacentric elements, form of the Y-chromosome, and C-banding pattern (Baskevich and Orlov, 1993; Lavrenchenko et al., 1998a). Analyses of allozymic and morphometric data indicate M. awashensis is more closely related to M. erythroleucus than to M. natalensis, but M. awashensis and M. natalensis are more similar in chromosomal traits and configuration of tail scales; in glans penis morphology, M. awashensis differs from either of the other species, which are similar in that character complex (Lavrenchenko and Baskevich, 1996; Lavrenchenko et al., 1998a). Mastomys awashensis shares a common fixed hemoglobin electromorph with South African M. coucha, different from that found in Ethiopian M. natalensis and M. erythroleucus (Lavrenchenko et al., 1992, 1998a). Those latter authors noted that the discordance among morphometric, genital, molecular, and chromosomal character suites in distinguishing samples of the three Ethiopian species may reflect a mosaic pattern of evolution. Character discordance, however, has not been an unappreciated reality to generations of working systematists, as many morphologically similar sets of species can only be distinguished by a combination of traits.

Yalden and Largen (1992) claimed that mammalian endemics of Ethiopia are associated with open habitats at high altitude or with forest blocks and are not found in the Awash Valley and other dry lowlands. Lavrenchenko et al. (1998a:49) used the occurrence of M. awashensis and a species of Acomys (uniquely defined by chromosomal traits according to Sokolov et al., 1993) in the upper Awash Valley as exceptions to Yalden and Largen’s proclamation, noting that the valley "with its unique rodent fauna is an integral part of the Ethiopian region with high faunistic diversity and endemism."