Streamflow trend analyses provide water managers with a tool for planning and predictions. Using multiple methods, we analyzed streamflow trends from 1996 to 2022 for the Southern Appalachian (SA) region of the U.S. The forested uplands of the SA receive high amounts of precipitation and act as a “water tower” for the surrounding lowland area, both of which have experienced higher than average population growth. For USGS gages in the area with continuous streamflow measurements (168 total), we also evaluated precipitation trends with the same methods, and land cover change and complexity (LCCC) rates within the area upstream of the gage (or contributing area). Generalized linear models were then used to assess any linkages between landscape variables and precipitation trends, and streamflow trends. Our results show that all basins are experiencing streamflow trends in at least one metric, with the ITA method showing the most trends and the SMK method showing the least. We also found that many drainage areas are experiencing trends in their precipitation and change in their land cover and complexity. From our models, it is suggested that reforestation, urbanization, and wetland loss to agriculture are all associated with monthly minimum and maximums and seasonal variability trends, but precipitation is also positively linked. These streamflow metrics and precipitation trends point towards depleted high-flow magnitude, reduced annual variability of high flows, erratic flows, and urban influences.