This systematic study documents the taxonomy, diversity, and distribution of the tarantula spider genus Aphonopelma Pocock, 1901 within the United States. By employing phylogenomic, morphological, and geospatial data, we evaluated all 55 nominal species in the United States to examine the evolutionary history of Aphonopelma and the group’s taxonomy by implementing an integrative approach to species delimitation. Based on our analyses, we now recognize only 29 distinct species in the United States. We propose 33 new synonymies (A. apacheum, A. minchi, A. rothi, A. schmidti, A. stahnkei = A. chalcodes; A. arnoldi = A. armada; A. behlei, A. vogelae = A. marxi; A. breenei = A. anax; A. chambersi, A. clarum, A. cryptethum, A. sandersoni, A. sullivani = A. eutylenum; A. clarki, A. coloradanum, A. echinum, A. gurleyi, A. harlingenum, A. odelli, A. waconum, A. wichitanum = A. hentzi; A. heterops = A. moderatum; A. jungi, A. punzoi = A. vorhiesi; A. brunnius, A. chamberlini, A. iviei, A. lithodomum, A. smithi, A. zionis = A. iodius; A. phanum, A. reversum = A. steindachneri), 14 new species (A. atomicum sp. n., A. catalina sp. n., A. chiricahua sp. n., A. icenoglei sp. n., A. johnnycashi sp. n., A. madera sp. n., A. mareki sp. n., A. moellendorfi sp. n., A. parvum sp. n., A. peloncillo sp. n., A. prenticei sp. n., A. saguaro sp. n., A. superstitionense sp. n., and A. xwalxwal sp. n.), and seven nomina dubia (A. baergi, A. cratium, A. hollyi, A. mordax, A. radinum, A. rusticum, A. texense). Our proposed species tree based on Anchored Enrichment data delimits five major lineages: a monotypic group confined to California, a western group, an eastern group, a group primarily distributed in high-elevation areas, and a group that comprises several miniaturized species. Multiple species are distributed throughout two biodiversity hotspots in the United States (i.e., California Floristic Province and Madrean Pine-Oak Woodlands). Keys are provided for identification of both males and females. By conducting the most comprehensive sampling of a single theraphosid genus to date, this research significantly broadens the scope of prior molecular and morphological investigations, finally bringing a modern understanding of species delimitation in this dynamic and charismatic group of spiders.