Groundwater‐surface water interactions (GSI) connect rivers and streams with riparian areas and the adjacent aquifer. Although these interactions exert a substantial control of quantity and quality of both groundwater and surface water, knowledge on GSI along rivers at the regional scale, particularly for inland waterways, is still limited. We investigated GSI along the river Moselle, an important federal inland waterway in Germany, by using radon and tritium to identify gaining (water flux from the aquifer to the surface water) and losing (water flux from the surface water to the aquifer) stream conditions, respectively. Gaining stream conditions were identified by continuously measuring radon along the river during boat surveys with a high spatial resolution (every 2 km) during intermediate (October 2020) and near low flow conditions (August/September 2021). The tritium concentrations in surface water and groundwater and the resulting tritium inventories were used to characterize losing stream conditions Monthly tritium inventories from 2017 to 2022 revealed a mean loss for the whole period of 20.3 % and a mean gain of 21.8%. Both were probably triggered by a combination of losing stream conditions and flood‐induced mass transfer of water from the aquifer back into the river as well as discharge fluctuations. At the investigated site Lehmen there were direct indications of an influence of surface water due to elevated tritium concentrations in the groundwater (up to 13.3 Bq L−1). Using radon mass balance modelling, good agreements of simulated versus measured radon data with respect to two groundwater end‐member scenarios were obtained during intermediate flow (Spearman's ρ: 0.97 and 0.99; MAE: 10.1 and 3.4 Bq L−1) and near low flow (Spearman's ρ: 0.97 and 0.99; MAE: 11 and 6.5 Bq L−1). Considerable groundwater inflow was limited to the meander of Detzem, where cumulated groundwater inflow of about 19 m3 s−1 (9.5% of total discharge) and 4.2 m3 s−1 (3.8% of total discharge) was simulated during intermediate and near low flow, respectively. However, the groundwater inflow was relatively low compared to alpine streams, for example. The study will help to better identify and quantify GSI at the regional scale and provide methodological guidance for future studies focusing on inland waterways.