Most terrestrial large mammals went extinct on different continents at the end of the Pleistocene, between 50,000 and 10,000 years ago. Besides the loss in species diversity and the truncation of body mass distributions, those extinctions were even more impactful to interaction diversity. Along with each extinction, dozens of ecological interactions were lost, reorganizing species interaction networks, which attained species-poor configurations with low functional redundancy. Extinctions of most large herbivores impacted energy flow and the rates of nutrient cycling, reconfiguring ecosystem-level networks. Because large mammals have high mobility, their loss also shortened seed-dispersal distance and reduced nutrient diffusivity, disrupting spatial networks. This review examines the recent advances in understanding how different types of ecological networks have been restructured by megafaunal extinctions and how this reorganization affected ecosystem functions. ▪Megafaunal extinctions resulted in the loss of multiple ecological interactions in terrestrial systems.▪Interaction loss reshaped different types of ecological networks including food webs and spatial networks.▪The reorganization of ecological networks changed how terrestrial ecosystems are structured and function.