Droughts lead to falling river water levels and consequently expose river sediments. It is well known that from these exposed aquatic sediments, CO2 emits to the atmosphere, but upscaling of CO2 measurements from discrete point measurements to an entire river system remains challenging. Naturally occurring heterogeneous processes must be accounted for to obtain an overall CO2 flux and to assess its significance. We contribute to this challenge by incorporating a two stage scaling approach using in situ CO2 fluxes and remote sensing data. First, by combining optical airborne data with closed chamber measurements at a representative model site during a first scaling stage, we derive land cover type specific CO2 fluxes and identify distance to the water as the most suitable proxy for further upscaling. Second, we upscale derived spatial relations from the first scaling stage to the entire river system of the Elbe River using a satellite‐based analysis. In this way, we derived area‐weighted CO2 emissions from exposed river sediments of 56.6 ± 64.8 tC day−1 (corrected distance proxy) and 52.9 ± 44.6 tC day−1 (land cover proxy), respectively, for 1 day during the 2018 extreme drought. Given the intensification of droughts in terms of length and reoccurrence frequency, this result not only highlights the importance of drought‐induced exposition of river sediment as a source of atmospheric CO2 but also underscores the ability to monitor CO2 emissions over an entire river system on a regular basis using remote sensing.