The impact of natural disasters and climate change on archaeological resources has garnered much recent attention, with impacts of sea level rise and coastal flooding being the two most often cited issues. However, damage caused by flooding of interior areas and waterways has received less consideration. In this article, we present a case study of a collaborative emergency response to a significant weather event and the ensuing impacts on archaeological resources. Our project, located in Middle Tennessee, documented severe erosion and subsequent anthropogenic disturbances to ancient Native American sites following massive flooding of the Cumberland River in 2010. While striving to mitigate this damage via systematic collection of imperiled archaeological samples, we were also able to strengthen partnerships among professional archaeologists working in different arenas (academia, state and federal agencies) and the avocational archaeological community. As these types of weather-related events become more common, published case studies of response efforts will be crucial in archaeological site management, planning, and disaster response.