The genus-level classification of soft ticks (Argasidae) is controversial. A previous phylogenetic analysis of morphological and developmental characters found that the genus Ornithodoros was paraphyletic and raised a new genus, Carios, for species previously in the genera Antricola, Argas, Ornithodoros, and Nothoaspis (Klompen and Oliver, 1993). Genetic analyses of soft ticks to date have been limited to 16S rRNA, which is not highly phylogenetically informative for this group. We sequenced the entire mitochondrial genomes of 7 species of soft ticks, and the partial mitochondrial genomes of a further 5 species of soft ticks. We used these sequences to test the genus-level classification of soft ticks. Our analyses strongly support a clade of Neotropical species (mostly bat-associated) within the subfamily Ornithodorinae. This clade, which we call Neotropical Ornithodorinae, has species from 2 genera, Antricola and Nothoaspis, and 2 subgenera, Ornithodoros (Alectorobius) and Ornithodoros (Subparmatus). We also addressed the phylogenetic position of Ornithodoros savignyi, the type species of the genus Ornithodoros. Our analysis strongly supports a clade consisting of Ornithodoros savignyi and 4 other Ornithodoros species: Or. brasiliensis, Or. moubata, Or. porcinus, and Or. rostratus. This clade, Ornithodoros sensu stricto, did not contain the Alectorobius and Subparmatus species, Or. (Alectorobius) fonsecai, Or. (Alectorobius) capensis, and Or. (Subparmatus) marinkellei, which in traditional classification schemes have been placed in the genus Ornithodoros. Our comparison of mitochondrial rRNA, nuclear rRNA, and mitochondrial genome analyses show that only mitochondrial genome sequences have the potential to resolve the controversial phylogenetic relationships within the major soft tick lineages, such as the taxonomic status of Carios sensu Klompen and Oliver (1993).