A global increase in megafires has occurred since the mid-1990s. Defined as wildfires that burn more than 405 km2 (100 000 ac), megafires are complex phenomena with wide ranging societal impacts. In the United States, scientific literature and wildland fire policy has traditionally focused upon megafires in forests of the American West. However, megafires also pose a significant threat to life and property on the southern Great Plains. The southern Great Plains is characterized by grass-dominated prairie and is climatologically prone to dry and windy weather, which facilitates extreme rates of fire spread leading to some of the largest wildfires in North America. This study documents 16 megafires on the plains of New Mexico, Texas, Oklahoma, and Kansas between 2006 and 2018. Most of these megafires occurred during southern Great Plains wildfire outbreaks, or plains firestorms, characterized by fire-effective low-level thermal ridges. Fuel and weather conditions supporting the 2006–2018 plains megafires are quantified by antecedent precipitation anomalies, fuel moisture, Energy Release Component, relative humidity, sustained wind speed, and temperature percentiles. Three modes of plains megafire evolution are identified by the analyses as short-duration, long-duration, and hybrid. Abrupt wind shifts and carryover fire in heavy dead fuels dictate megafire potential and evolutionary type. The presented analyses define favorable fuel and weather conditions that allow forecasters to discriminate megafire environments from typical plains fire episodes. Further, predictive signals for plains megafire conceptual model types can improve anticipation of southern Great Plains megafire evolution, threats, and management strategies.