Ecomorphological studies often seek to link morphology and performance to relevant ecological characteristics. Varanid lizards are unique in that species can vary in body size by almost four orders of magnitude within a single genus, and a question of considerable interest is whether similar ecomorphological relationships exist when constraints on body size are reduced. We studied sprint speed in relation to size, shape and ecology for 18 species of varanid lizards. Maximal speed scaled positively with mass0.166 using least squares regression, and mass0.21 using reduced major-axis regression. However, a curvilinear trend better described this relationship, suggesting an optimal mass of 2.83 kg with respect to speed. Including data for the komodo dragon Varanus komodoensis moves the optimum mass to 2.23 kg. We use this relationship to predict the sprint speed of the Komodo's giant extinct relative Varanus (Megalania) prisca to be 2.6–3 m s−1 similar to that of extant freshwater crocodiles Crocodylus johnstoni. When differences in speed were compared to ecological characteristics, species from open habitats were significantly faster than species from semi-open or closed habitat types, and remained so after correction for size and phylogeny. Thus, despite large variation in body size, varanids appear to share similar associations between performance and ecology as seen in other lizard groups. Varanids did, however, differ in morphological relationships with sprint speed. Differences in relative speed were not related to relative hindlimb length, as is commonly reported for other lizard groups. Instead, size-free forefoot length was negatively related to speed as was the size-free thorax–abdomen length. While shorter forefeet were thought to be an adaptation to burrowing, and thus open habitats, rather than speed per se, the reduction in the thorax–abdomen length may have significant advantages to increasing speed. Biomechanical models predicting this advantage are discussed in relation to a trade-off between speed and manoeuvrability.