The vertebrate skull has undergone periods of bone loss or fusion throughout its evolution, particularly at the origin of major clades. This trend, known as “Williston’s Law ”, has been suggested to result in more mechanically efficient skulls. The origin of tetrapods occurred alongside major changes in cranial structure, which have been linked to consolidation of the skull as feeding mode changed across the water-to-land transition. It has therefore been inferred, but not tested, that Williston’s Law explains changes in skull anatomy across this major event in vertebrate evolution. We quantified skull architecture across the water-to-land transition, using a network-based approach to analyse topological features of 17 ‘fish’ and 93 tetrapod skulls. Moreover, this large sample allowed us to quantify the evolution of the structural disparity of the skull from the Early Devonian to the present day. We found that skull architecture changes significantly across the water-to-land transition, showing increased topological complexity and decreased modularity. This suggests that bone loss and fusion lead to greater connectivity among the remaining elements, disputing the assumption that Williston’s Law leads to anatomical simplification. We found that skull topological disparity decreases at the origin of Tetrapoda, followed by a second significant drop at the end of the Devonian congruent with the Hangenberg extinction event and continuing into Romer’s gap. We therefore conclude that the architecture of tetrapod skulls has been shaped by both mechanical constraints associated with bone loss as well as influence from external extinction and diversification events.