Investigations carried out on 72 fluid samples from 59 sites spread over the area surrounding the Sea of Marmara show that their geochemical and isotopic features are related to different segment settings of the North Anatolian Fault Zone (NAFZ). We collected fluids from thermal and mineral waters including bubbling and dissolved gases. The outlet temperatures of the collected waters ranged from 14 to 97 °C with no temperature-related geochemical features. The free and dissolved gases are a mixture of shallow and mantle-derived components. The large variety of geochemical features comes from intense gas–water (GWI) and water–rock (WRI) interactions besides other processes occurring at relatively shallow depths. CO2 contents ranging from 0 to 98.1% and helium isotopic ratios from 0.11 to 4.43 Ra indicate contributions, variable from site to site, of mantle-derived volatiles in full agreement with former studies on the NAFZ. We propose that the widespread presence of mantle-derived volatiles cannot be related only to the lithospheric character of the NAFZ branches and magma intrusions have to be considered. Changes in the vertical permeability induced by fault movements and stress accumulation during seismogenesis, however, modify the shallow/deep ratio of the released fluids accordingly, laying the foundations for future monitoring activities.