We present an overview of genome-level analysis, including morphological diversities, comparative genomics, evolution, introgression, and breeding potential to Gossypium subgenus Houzingenia. This framework facilitates insight into plant genome research and lays the foundation for effective utilization of genetic resources in Houzingenia. To date, these 14 species-containing subgenera have been designated as D1- to D12-genomes, with two D2- and two D3-genomes, respectively. The D5-genome named Gossypium raimondii is known as the closest living ancestor of the D-subgenome of wild and domesticated allotetraploid cottons. Since the release of G. raimondii as the first cotton genome in 2012, the genomes for most Houzingenia subgenus species have been sequenced, successfully assembled, and publicly available. This subgenus diverged with other cotton species at 2–13 million years ago (MYA) and experienced subsequent diversification events at ~0.5–3.3 MYA. Molecular evidence supports a monophyletic origin of the subgenus that can be further divided into six closely related subsections. The subsection Selera (Gossypium gossypioides) is located at the most basal position within the subgenus and diverged early on along with other D-genomes at ~2.9–3.6 MYA. Molecular evidence also clarified that G. raimondii is the basal clade of five sequenced allotetraploid cottons, which bolsters the view that G. raimondii is the D-subgenome donor. Overall, the genomes of subgenus Houzingenia have undergone only slight divergence and their genomes are relatively stable, but these species have maintained abundant genetic diversity and a number of desirable genetic traits that will potentially be used by cotton breeders to improve agronomical productivity or fiber quality in cultivated G. hirsutum and/or G. barbadense.