We used nucleotide sequences from four mitochondrial genes and structural features of the mitochondrial control region, combined with a revised, previously published, morphological data set to infer phylogenetic relationships among the pythons. We aimed to determine which of two competing hypotheses of relationships of the genera Aspidites and Python best explains the evolutionary and bioegeographical history of the family. All analyses of the combined data recover a set of relationships in which (1) the genus Python is paraphyletic with the two east Asian species, P. reticulatus and P. timoriensis, as the sister lineage to the seven Australo-Papuan python genera. We support recognition of a distinct genus for the P. reticulatus + P. timoriensis clade; (2) the remaining species of the genus Python form a clade which is the sister lineage to the remainder of the family; (3) the genus Aspidites is embedded among the Australo-Papuan genera. The seemingly primitive characteristics of Aspidites may be better interpreted as reversals or specializations that have accompanied a switch to burrowing in this genus. Resolution of the relationships among the Australo-Papuan lineages is weak, possibly because of rapid diversification early in the history of the radiation. We assessed the tempo of the Indo-Australian python radiation using a maximum likelihood framework based on the birth–death process. We find strong support for elevated speciation rates during the period when Australia collided with the proto-Indonesian archipelago. The data support an origin for pythons outside Australia, followed by a radiation into Australia during the mid-Tertiary. © 2008 The Linnean Society of London, Biological Journal of the Linnean Society, 2008, 93, 603–619.