We investigated the rate‐and‐state frictional properties of simulated anhydrite‐carbonate fault gouge derived from the basal Zechstein caprock overlying the seismogenic Groningen gas reservoir in the NE Netherlands. Direct shear experiments were performed at in situ conditions of 50–150 °C and 40‐MPa effective normal stress, using sliding velocities of 0.1–10 μm/s. Reservoir pore fluid compositions were simulated using 4.4 Molar NaCl brine, as well as methane, air, and brine/gas mixtures. Brine‐saturated samples showed friction coefficients (μ) of 0.60–0.69, with little dependence on temperature, along with velocity strengthening at 50–100 °C, transitioning to velocity weakening at 120 °C and above. By contrast, gas filled, evacuated and partially brine‐saturated samples showed μ values of 0.72 ± 0.02 plus strongly velocity‐weakening behavior accompanied by stick slip at 100 °C (the only temperature investigated for gas‐bearing and dry samples). A microphysical model for gouge friction, assuming competition between dilatant granular flow and thermally activated compaction creep, captures the main trends seen in our brine‐saturated samples but offers only a qualitative explanation for our gas‐bearing and dry samples. Since the reservoir temperature is ~100 °C, our results imply high potential for seismogenic slip nucleation on faults that cross cut and juxtapose the basal Zechstein anhydrite‐carbonate caprock against the Groningen reservoir sandstone, specifically in the gas‐filled upper portion of the reservoir system.