Mosaic evolution occurs when there are differential rates of evolution across different organismal traits. Flatfishes (Pleuronectiformes: Teleostei) exhibit striking cranial asymmetry that results from the migration of one of their eyes to the opposite side of their head during development. The developmental sequence of orbital migration has also been found to recapitulate the evolutionary transition towards asymmetry in the fossil record. However, the evolutionary tempo and mode of this orbital migration has yet to be examined in a rigorous quantitative phylogenetic comparative framework. Here we use three-dimensional geometric morphometrics and a phylogenetic comparative toolkit to examine evolutionary patterns of shape variation across 92 species of flatfishes and their relatives, and compare rates of shape evolution between different regions of the skull. We find that flatfishes on average, exhibit a 14-fold increase in their rates of skull shape evolution relative to non-flatfishes. We also find mosaic patterns of shape evolution across the skull, with the orbital and frontal regions evolving more quickly than the dorsal elements of the braincase. Interestingly, we recover rapid rates of shape evolution in the basicranium, and reduced rates of shape evolution in the most anterior regions of the skull (e.g. ethmoid region). We hypothesize that the orbital migration (localized to middle portion the skull) of flatfishes, is responsible for driving the mosaic patterns of shape evolution observed in this clade of fishes.