Invasive species are a threat to biodiversity, and understanding their impacts on native ecosystems is a research priority. Red Imported Fire Ants (Solenopsis invicta) are invasive in the southeastern United States and have multiple effects on a variety of native species. Some species and particular life stages (e.g., juveniles and eggs), may be especially vulnerable to fire ants, but research on these impacts has been limited. Fire ants occupy microhabitats used for nesting by Eastern Fence Lizards (Sceloporus undulatus) across much of their range. We examined the extent of fire ant predation on fence lizard eggs by constructing artificial nests at a fire ant–invaded location and monitoring their predation for up to 20 days. During this period, 24% of nests were predated by fire ants, and survival curves suggest 61% of nests may be vulnerable to fire ant predation over the entire incubation period. Distance of nests to the nearest fire ant mound and canopy cover above nests were not significant predictors of predation, indicating that nest site choice by fence lizards may not be able to avert fire ant predation. Invasive fire ants likely represent a novel level of predation pressure on many species, and these effects should be accounted for in management and conservation strategies.