This species is an inhabitant of Madagascar’s eastern lowland forests where conditions of water and food availability are not as seasonally severe as in the drier western deciduous forests. During the active season, this species occupies tree holes or nest-like structures (Blanco, per.obs., Lahann 2007). The species prepares for hibernation by storing excess fat in its tail, but they have shorter hibernation periods than other dwarf lemur species. Cheirogaleus major hibernates inside tree holes and/or underground burrows (Blanco et al. 2018). Home ranges of adult females extend ~4 ha and appear to include those of adult males and juveniles as well (Lahann 2007). Sleeping groups of up to three adult animals have been observed both in tree holes and clumps of vegetation. Mating behaviour ensues shortly after emergence from torpor in October and November, females giving birth to two to three infants in January after a gestation of about 70 days (Petter-Rousseaux 1964). However, a number of observations of this species, cited here and elsewhere in this account, were made in Andasibe (= Périnet), and probably refer to C. crossleyi.

This species is found in north-eastern, eastern-central and south-eastern Madagascar. In the north-east, Cheirogaleus major has been found at Marojejy National Park, Makirovana-Tsihomanaomby complex, Masoala and Makira (Blanco, pers. obs., Brooke et al. in press, Williams et al. 2019). In the eastern rainforests, it has been found in Mananara, Tampolo, Sahafina and Andasibe (Lei et al., 2014, McLain et al, 2017, Razafindrasolo, pers. obs.) According to Groeneveld et al. (2009), C. major is found from the south-eastern tip of the island near Tolagnaro (= Fort-Dauphin) potentially all the way up to near the northern tip, with an additional, small population isolate in the central-west. The southern limit of its distribution is particularly interesting, since two other dwarf lemur species can also be found in the same general region, although not to date in the same forests. Andreas Hapke has found C. major in the humid forests of the Vohimena and Anosy mountains and the littoral forest at Mandena, and believes it might also occur in Sainte-Luce, but this has yet to be confirmed (Hapke et al. 2005). C. major generally occupies low elevation rainforests, whereas C. crossleyi can occupy low as well as high elevation sites. These species can be found to live in sympatry (Williams et al. 2019).

This species is likely affected by national trends in forest habitat loss: Madagascar lost 37% of its forest cover from 1973 to 2014, with an annual deforestation rate of 1.1%/year from 2010 to 2014. Almost half of Madagascar's forest (46%) is now located within less than 100 metres from the forest edge (Vieilledent et al. 2018). C. major shows a negative edge effect (densities are lower in closer proximity to the forest edge) (Lehman et al. 2007).

This species is listed on Appendix I of CITES. This species is relatively widespread but additional taxonomic revision is pending. It is reported to occur in four national parks: Andasibe-Mantadia, Mananara-Nord, Marojejy, Masoala, one strict nature reserve, Betampona and Makira Natural Park, as well as in the Mandena Conservation Zone, east of Tolagnaro. More recently, based on genetic analysis, Cheirogaleus major has been found in Makirovana/Tsihomanaomby (NE Madagscar) living in sympatry with C. medius-like and C. crossleyi. The population of C. major at Tsihomanaomby, however, differs morphologically from that of Marojejy National Park, particularly in fur coloration, with more grey-brownish coat in the former compared to reddish-brownish in the latter (Blanco, pers. obs., Williams et al. 2019). Population densities in some of these locations seem to be comparatively low, and C. major shows a negative edge effect (densities are lower in closer proximity to the forest edge) (Lehman et al. 2007).