Competition between native and alien species is often described as a main driver of biodiversity loss. Nevertheless, there is limited evidence of animal declines and extinctions actually determined by competition. The Aeolian lizard, Podarcis raffonei, is critically endangered because it suffered dramatic declines and extinctions throughout its range. Competition and hybridization with invasive Italian lizards, Podarcis siculus, have been proposed as a driver of the shrinkage of Aeolian lizards, still the mechanisms underlying their decline remain poorly resolved. We used observations of behavioral encounters, combined with morphological data and robust species identification based on genomics, to test whether agonistic interactions with the invasive Italian lizard can explain the competitive exclusion and rapid decline of the native Aeolian lizard while accounting for hybridization. Invasive lizards were larger, with larger heads, and showed higher bite tendency against neutral items. In agonistic encounters between males, Aeolian lizards received more attacks and escaped more frequently than invasive males. The performance of Aeolian males was particularly poor in interspecific encounters. Genomic data verified that tested individuals were all pure P. raffonei or P. siculus, with a single hybrid individual detected. The strong competitive advantage of invasive males can allow them monopolizing territories, potentially hampering the reproduction of both native males and females, thus resulting in a mechanism of sterilizing interference. Reproductive interference competition mediated by spatial exclusion might be an unappreciated process determining rapid decline in endemic species. Safeguarding areas devoid of invasive species should be the priority strategy to avoid the extinction of the Aeolian lizards.