The U.S. Geological Survey (USGS) long-term daily streamflow record at station 02173000 in Bamberg County, South Carolina on the South Fork Edisto River (Latitude 33°23’35”, Longitude 81°08’00” NAD27) spans from 1932 to 2015 and was used for this study. The Nature Conservancy’s Indicators of Hydrologic Alteration (IHA) software was used to analyze the entire record of hydrologic data as ecologically relevant parameters and to categorize the flows. A two-period analysis was conducted to evaluate whether a significant difference could be observed in historic flow data from 1932–1985 (period one) compared to 1986–2015 (period two). An extreme low flow was defined as an initial low flow below 10% of daily flows for the period. Over the entire 76-year period of record, 51 years had at least one occurrence of extreme low flows. A median of 4 days per year had occurrences of extreme flows in period one in contrast to a median of 60 days per year during period two. Annual precipitation totals were not correlated with the number of days per year with extreme low flows. The two-period analysis showed significant differences between period one and period two for monthly mean flow for February, April, May, and August, as well as for 1-day and 30-day minima and maxima values. The analysis calculated the 7Q10 (the lowest stream flow for seven consecutive days that would be expected to occur once in ten years) at 4.4 cubic meters per second (cms), which was -10.9% different from the most recently published estimate. Results presented in this study have shown that spring and summer flows in the South Fork Edisto are statistically significantly lower in period two compared to period one.