A polymorphic inversion that lies on chromosome 17q21 comprises two major haplotype families (H1 and H2) that not only differ in orientation but also in copy-number. Although the processes driving the spread of the inversion-associated lineage (H2) in humans remain unclear, a selective advantage has been proposed for one of its subtypes. Here, we genotyped a large panel of individuals from previously overlooked populations using a custom array with a unique panel of H2-specific single nucleotide polymorphisms and found a patchy distribution of H2 haplotypes in Africa, with North Africans displaying a higher frequency of inverted subtypes, when compared with Sub-Saharan groups. Interestingly, North African H2s were found to be closer to "non-African" chromosomes further supporting that these populations may have diverged more recently from groups outside Africa. Our results uncovered higher diversity within the H2 family than previously described, weakening the hypothesis of a strong selective sweep on all inverted chromosomes and suggesting a rather complex evolutionary history at this locus. ; IPATIMUP integrates the i3S Research Unit, which is partially supported by FCT, the Portuguese Foundation for Science and Technology. This work is also partially funded by FEDER funds through the Operational Programme for Competitiveness Factors—COMPETE and National Funds through the FCT—Foundation for Science and Technology, under the project “PEst-C/SAU/LA0003/2013.” IPATIMUP is also supported by NORTE-07-0162-FEDER-00018 and NORTE-07-0162-FEDER-000067, under Programa Operacional Regional do Norte (ON.2—O Novo Norte), through FEDER funds under the Quadro de Referência Estratégico Nacional (QREN). J.M.A. is funded by a doctoral fellowship from FCT (SFRH/BD/51004/2010) and a European Molecular Biology Organization (EMBO) short-term fellowship (ASFT 520-2013). A.C.L. is funded by an FCT doctoral fellowship (SFRH/BD/51695/2011). D.C. was funded by a Spanish MINECO project (CGL2013-44351-P). L.C. is partly funded by the Laboratoire d’Excellence (LABEX) entitled TULIP (ANR-10-LABX-41) and by the FCT project (PTDC/BIA-BIC/4476/2012). A.M.L. is the recipient of a research contract from FCT (IF/01262/2014)