Rivers represent a transition zone between terrestric and aquatic environments, and between methane rich and methane poor environments. The Elbe River is one of the most important rivers draining into the North Sea and, along with the Elbe, a potential importer of high amounts of methane into the water column of the North Sea. Twelve sampling cruises from October 2010 until June 2013 were conducted from Hamburg towards the mouth of the Elbe at Cuxhaven. The dynamic of methane concentration in the water column and its consumption via methane oxidation was measured. In addition, physico-chemical parameters were used to estimate their influence on the methanotrophic activity. We observed high methane concentrations at the stations in the area of Hamburg harbor (“inner estuary”) and about 10 times lower concentrations in the outer estuary (median of 416 versus 40 nmol/L, respectively). The methane oxidation (MOX) rate mirrored the methane distribution with high values in the inner estuary and low values in the outer estuary (median of 161 versus 10 nmol/L/d, respectively). Methane concentrations were significantly influenced by the river hydrology (falling water level) and the trophic state of the water (biological oxygen demand). In contrast to other studies no clear relation to the amount of suspended particulate matter (SPM) was found. Methane oxidation rates were significantly influenced by methane concentration and to a lesser extent by temperature. Methane oxidation accounted for 41 ± 12% of the total loss of methane in the summer/fall, but for only 5 ± 3% of the total loss in the winter/spring. We applied a modified box model taking into account the residence times of each water parcel depending on discharge and tidal impact. We observed almost stable methane concentrations in the outer estuary, despite a strong loss of methane through diffusion and oxidation. Thus, we postulate that the water column undergoes a balancing out in the outer Elbe estuary due to a strong additional input of methane, which could be provided by the extensive salt marshes near the river mouth.