ABSTRACT: Members of the predatory Myxococcales (myxobacteria) possess large genomes, undergo multicellular development, and produce diverse secondary metabolites, which are being actively prospected for novel drug discovery. To direct such efforts, it is important to understand the relationships between myxobacterial ecology, evolution, taxonomy, and genomic variation. This study investigated the genomes and pan-genomes of organisms within the Myxococcaceae, including the genera Myxococcus and Corallococcus, the most abundant myxobacteria isolated from soils. Previously, ten species of Corallococcus were known, whereas six species of Myxococcus phylogenetically surrounded a third genus (Pyxidicoccus) composed of a single species. Here, we describe draft genome sequences of five novel species within the Myxococcaceae (Myxococcus eversor, Myxococcus llanfairpwllgwyngyllgogerychwyrndrobwllllantysiliogogogochensis, Myxococcus vastator, Pyxidicoccus caerfyrddinensis, and Pyxidicoccus trucidator) and for the Pyxidicoccus type species strain, Pyxidicoccus fallax DSM 14698T. Genomic and physiological comparisons demonstrated clear differences between the five novel species and every other Myxococcus or Pyxidicoccus spp. type strain. Subsequent analyses of type strain genomes showed that both the Corallococcus pan-genome and the combined Myxococcus and Pyxidicoccus (Myxococcus/Pyxidicoccus) pan-genome are large and open, but with clear differences. Genomes of Corallococcus spp. are generally smaller than those of Myxococcus/Pyxidicoccus spp. but have core genomes three times larger. Myxococcus/Pyxidicoccus spp. genomes are more variable in size, with larger and more unique sets of accessory genes than those of Corallococcus species. In both genera, biosynthetic gene clusters are relatively enriched in the shell pan-genomes, implying they grant a greater evolutionary benefit than other shell genes, presumably by conferring selective advantages during predation.