Groundwater pumping-induced reductions in streamflow (known as ‘streamflow depletion’) have been documented worldwide, but potential impacts of streamflow depletion on water quality indicators like stream temperature are not well understood. Here, we aim to identify potential impacts of pumping on stream temperature across the conterminous United States (CONUS) to determine which aspects of a stream’s annual thermograph, which we term thermohydrologic signatures, can be used to monitor and manage streamflow depletion impacts on stream temperature. We used long-term streamflow and stream temperature data from 46 streamgages across CONUS and archetypal models of streamflow depletion to analyze stream temperature impacts for dry, average, and wet conditions at each site. We compared two different stream temperature modeling approaches: (i) a 1-D energy balance model and (ii) statistical regression models based on air temperature and stream discharge. We calculated a suite of thermohydrologic signatures under depleted and non-depleted conditions for each stream and found that maximum annual 7-day temperature and annual temperature range are most sensitive to streamflow depletion, with potential changes of at least 2°C at >50% of the sites when using the physically-based model. We also found that the regression-based models predicted much less sensitivity of stream temperature to streamflow depletion than the physically-based model. Potential impacts were then estimated for 8,933 streamgages across CONUS using random forest models developed for each thermohydrologic signature. Potential streamflow depletion impacts on maximum 7-day temperatures are most common in northern CONUS where groundwater temperatures are cold (<15°C) and baseflow index is high (>50%). This work provides a systematic evaluation of the potential impacts of streamflow depletion on stream temperature.