Although artificial islands are often formed as a consequence of anthropogenic impacts in ecosystems, they provide opportunities to test some traditional assumptions of the theory of Biogeography of Islands and further effects of habitat fragmentation. Since 1996 we conducted studies focusing on how the formation of small artificial islands affects the ecology of Cerrado lizards. The Serra da Mesa reservoir, formed in October 1996, is the largest in water volume and the fourth in surface area in Brazil. Before reservoir formation, we selected 10 hilltops for long-term monitoring. We conducted samplings from May 1996 to January 1999, from May to September 2001, from July to September 2011, and from June to July 2019. The regional pool was originally composed of 19 lizard species belonging to 10 families. The movement of lizards from valleys to higher areas during flooding caused a noticeable crowding and increased species richness on the hilltops. However, two species disappeared from islands in 1999. In 2001, the richness of islands was smaller compared to plots in reservoir margin but was twice abundant. At this moment, island lizards had a lower body condition than individuals in the margins but were not more asymmetrical. The species that declined or disappeared from islands were the largest and commonest before insularization. Island lizards had similar body condition to lizards in margins in 2011 but were more asymmetrical. In 2019, we found only five species on islands. The more resilient species in islands, the gecko Gymnodactylus amarali, presented rapid changes in morphology, ecology, and eventually in its genetics, caused by isolation. Island geckos have larger heads and wider niche breadth compared with margin individuals. They also presented distinct climatic-adapted SNPs compared to populations in near localities. Insularization caused deep changes in the diversity of Serra da Mesa lizards, reducing species richness, impoverishing communities, and affecting individuals’ fitness, performance, and survival. It also provoked rapid adaptations in morphology, ecology, and genetics of more resilient species, suggesting that some Cerrado lizards can respond quickly to anthropogenic changes, although we are convinced that we studied a vanishing fauna, in an extinction-debt context.