Mofettes are gas emission sites where high concentrations of CO2 ascend through conduits from as deep as the mantle to the Earth’s surface and as such provide direct windows to processes at depth. The Hartoušov mofette, located at the western margin of the Eger Graben, is a key site to study interactions between fluids and swarm earthquakes. The mofette field (10 mofettes within an area of 100 m × 500 m and three wells of 28, 108, and 239 m depth) is characterized by high CO2 emission rates (up to 100 t/d) and helium signatures with (3He/4He)c up to 5.8 Ra, indicating mantle origin. We compiled geological, geophysical, geochemical, and isotopic data to describe the mofette system. Fluids in the Cheb basin are mixtures between shallow groundwater and brine (>40 g/L at a depth of 235 m) located at the deepest parts of the basin fillings. Overpressured CO2-rich mineral waters are trapped below the mudstones and clays of the sealing Cypris formation. Drilling through this sealing layer led to blow-outs in different compartments of the basin. Pressure transients were observed related to natural disturbances as well as human activities. External (rain) and internal (earthquakes) events can cause pressure transients in the fluid system within hours or several days, lasting from days to years and leading to changes in gas flux rates. The 2014 earthquake swarm triggered an estimated excess release of 175,000 tons of CO2 during the following four years. Pressure oscillations were observed at a wellhead lasting 24 h with increasing amplitudes (from 10 to 40 kPa) and increasing frequencies reaching five cycles per hour. These oscillations are described for the first time as a potential natural analog to a two-phase pipe–relief valve system known from industrial applications.