D. melanogaster is cosmopolitan in its distribution, only not being found at extremes of altitude and latitude.  It is generally a synanthropic species, being found in close or reasonably close association with humans.

D. melanogaster is a member of the subgenus Sophophora of the genus Drosophila. The Sophophora include several major species-groups, of which the following are the largest: the melanogaster species-group, with a predominantly Oriental and Afrotropic distribution; the obscura species-group, predominantly Holarctic, and the Neotropical willistoni and saltans species-groups. The melanogaster species-group, with 180 or so described species is now considered to be divided into 12 species-subgroups, nearly all of which have an Oriental distribution. The melanogaster species subgroup is an exception, it is an Afrotropical group, with nine known members:

• D. melanogaster Meigen 1830
• D. simulans Sturtevant 1919
• D. yakuba Burla 1954
• D. teissieri Tsacas 1971
• D. erecta Tsacas and Lachaise 1974
• D. mauritiana Tsacas and David 1974
• D. orena Tsacas and David 1978
• D. sechellia  Tsacas and Bächli 1981
• D. santomea Lachaise et al. 1981

                                                                                   
A historical account of their discovery has recently been published by David et al. [16].

These nine species are sibling species, in the sense of Ernst Mayr, that is to say they are morphologically very similar, indeed the females cannot reliably be distinguished by their external characteristics. The males can, by the morphologies of their external genitalia.

Like D. melanogaster, D. simulans has a cosmopolitan distribution (though perhaps not as widespread as the former species). The other seven species are more restricted. D. yakuba and D. teissieri are widespread in sub-Saharan Africa, the former being a savannah species, the latter a forest species. D. santomea, very closely related to D. yakuba (with which it forms interspecific hybrids in the wild) is a montane species on the island of Sao Tome. D. erecta and D. orena are tropical west African species, the former specialized to the fruits of Pandanus, the latter only having been found once, on Mount Lefo in the Western Cameroon.  D. mauritiana and D. sechellia are insular species on their cognate Indian Ocean islands; the latter is specialized to breed in the foul-smelling fruits of the rubiaceous shrub Morinda citrifolia.

The phylogenetic relationships among these nine species is reasonably well understood, primarily from the analyses of their polytene chromosome banding patterns and from analyses of their DNA sequences.

The age of this small species-subgroup is estimated as about 20 MY, the founders of the subgroup having entered the Afrotropical Region from Eurasia, presumably across a landbridge after the closure of the Tethys Sea.