Haplogroup E-M2, also known as E1b1a1-M2, is a human Y-chromosome DNA haplogroup. E-M2 is primarily distributed within Africa followed by West Asia. More specifically, E-M2 is the predominant subclade in West Africa, Central Africa, Southern Africa, and the region of the African Great Lakes; it also occurs at moderate frequencies in North Africa, and the Middle East. E-M2 has several subclades, but many of these subhaplogroups are included in either E-L485 or E-U175. E-M2 is especially common among indigenous Africans who speak Niger-Congo languages, and was spread to Southern Africa and East Africa through the Bantu expansion.

The discovery of two SNPs (V38 and V100) by Trombetta et al. (2011) significantly redefined the E-V38 phylogenetic tree. This led the authors to suggest that E-V38 may have originated in East Africa. E-V38 joins the West African-affiliated E-M2 and the Northeast African-affiliated E-M329 with an earlier common ancestor who, like E-P2, may have also originated in East Africa. The downstream SNP E-M180 may have originated in the humid Saharan savanna/grassland of North Africa between 14,000 BP and 10,000 BP. According to Wood et al. (2005) and Rosa et al. (2007), such population movements changed the pre-existing population Y chromosomal diversity in Central, Southern, and Southeastern Africa, replacing the previous haplogroup frequencies in these areas with the now dominant E1b1a1 lineages. Traces of earlier inhabitants, however, can be observed today in these regions via the presence of the Y DNA haplogroups A1a, A1b, A2, A3, and B-M60 that are common in certain populations, such as the Mbuti and Khoisan. Shriner et al. (2018) similarly suggests that haplogroup E1b1a-V38 traversed across the Green Sahara from east to west around 19,000 years ago, where E1b1a1-M2 may have subsequently originated in West Africa or Central Africa. Shriner et al. (2018) also traces this movement via sickle cell mutation, which likely originated during the Green Sahara period.

At Xaro, in Botswana, there were two individuals, dated to the Early Iron Age (1400 BP); one carried haplogroups E1b1a1a1c1a and L3e1a2, and another carried haplogroups E1b1b1b2b (E-M293, E-CTS10880) and L0k1a2.

At Taukome, in Botswana, an individual, dated to the Early Iron Age (1100 BP), carried haplogroups E1b1a1 (E-M2, E-Z1123) and L0d3b1.

At Kindoki, in the Democratic Republic of Congo, there were three individuals, dated to the protohistoric period (230 BP, 150 BP, 230 BP); one carried haplogroups E1b1a1a1d1a2 (E-CTS99, E-CTS99) and L1c3a1b, another carried haplogroup E (E-M96, E-PF1620), and the last carried haplogroups R1b1 (R-P25 1, R-M415) and L0a1b1a1.

Hawass et al. (2012) determined that the ancient Egyptian mummy of an unknown man buried with Ramesses III was, because of the proven genetic relationship and a mummification process that suggested punishment, a good candidate for the pharaoh's son, Pentaweret, who was the only son to revolt against his father. It was impossible to determine his cause of death. Using Whit Athey's haplogroup predictor based on Y-STR values, both mummies were predicted to share the Y chromosomal haplogroup E1b1a1-M2 and 50% of their genetic material, which pointed to a father-son relationship. Gad et al. (2021) indicates that Ramesses III and Unknown Man E, possibly Pentawere, carried haplogroup E1b1a, which appears at its highest frequency rates in Central Africa at ~60% and in West Africa at ~80%.

During the 18th Dynasty of Ancient Egypt, some mummies from the Amarna Period carried haplogroups E1b1a and L.

At Deloraine Farm, in Nakuru County, Kenya, an iron metallurgist of the Iron Age carried haplogroups E1b1a1a1a1a/E-M58 and L5b1.