Given its singular importance for water resources in the southwestern U.S., the Upper Colorado River Basin (UCRB) is remarkable for the paucity of its conventional hydrological record of extreme flooding. This study uses paleoflood hydrology to examine a small portion the underutilized, but very extensive natural record of Holocene extreme floods in the UCRB. We perform a meta-analysis of 77 extreme paleofloods from seven slackwater deposit sites in the UCRB to show linkages between Holocene climate patterns and extreme floods. The analysis demonstrates several clusters of extreme flood activity: 8040-7790, 3600-3460, 2880-2740, 2330-700, and 620-0 years BP. The extreme paleofloods were found to occur during both dry and wet periods in the paleoclimate record. When compared with independent paleoclimatic records across the Rocky Mountains and the southwestern U.S., the observed temporal clustering pattern of UCRB extreme paleofloods shows associations with periods of abruptly intensified North Pacific-derived storms connected with enhanced El Niño variability.