Extreme floods are underrepresented in instrumented flow records. Consequently, flood frequency model estimates of extreme floods contain large uncertainty. The lower Tennessee River (LTR) Basin is located within the southeastern United States and is a large, regulated, and socio-economically significant North American river. The flood-of-record for the LTR occurred in 1867 CE. The 1867 flood-of-record is a design flow for the dams built and managed by the Tennessee Valley Authority. Here we develop and apply an extreme paleoflood chronology and use it to improve flood frequency model estimates of large, rare floods. We created an extreme paleoflood chronology that contained paleodischarge estimates for six extreme paleofloods, dating back to 5900 years before present, for a ∼2 km segment of the LTR. We obtained paleoflood hydrologic data from two sources. These included field sampling and analysis of slackwater deposits found in a rock shelter located on a limestone bluff and published extreme paleoflood data from a terrace located within the study segment.Placed within the context of the extreme paleoflood chronology, the 1867 flood-of-record was the largest flood to occur within the last 2000 years and coincided with the conclusion of the cooler, wetter Little Ice Age. The three highest magnitude extreme floods, however, occurred during a peak in Holocene temperatures 6000 to 5000 years ago, during the mid-Holocene Thermal Maximum. Paleodischarge estimates for the three mid-Holocene extreme floods were three times larger than the estimated discharge of the 1867 CE flood-of-record. Different iterations of a Bayesian flood frequency model showed removing the three most extreme, mid-Holocene paleofloods resulted in a rarer annual exceedance probability for the 1867 CE flood-of-record, changing it from an 0.002 AEP (500-year event) to an 0.0007 AEP (1300-year event) and underestimation of annual exceedance probabilities for design flows commonly used in river management and infrastructure design, including the 100-yr, 500-yr, 1000-yr, and 10,000-yr floods. These results suggest that flood frequency models may underestimate design flows if historic-floods-of-record are assumed to be the most extreme floods within these analyses. This finding has implications for regulated rivers worldwide, which now includes most large rivers. The previously unknown, extreme mid-Holocene paleofloods, which were found to be larger than all known modern or paleofloods, significantly altered the estimates of the final flood frequency model. This finding makes a compelling case for seeking out more extreme flood paleodischarge estimates from the mid-Holocene in rivers of the Northern Hemisphere, where the mid-Holocene Thermal Maximum's occurrence is well substantiated. Flood data from the mid-Holocene Thermal Maximum may help improve flood frequency model-based estimates of extreme floods by minimizing risk associated with flood “unknown unknowns.”