Water content (θ) and distribution are important parameters for landfill operators because θ is generally considered a key factor for the degradation of municipal solid waste (MSW) in landfills. This study investigated the applicability of time domain reflectometry (TDR) for the determination of θ. Although TDR is commonly applied to soils, only a few researchers have explored the sensitivity of its measurements to various parameters in MSW, which is a heterogeneous and time-evolving material. The aim of this study was to evaluate the calibration of TDR probes in MSW and to quantify the sensitivity of the method to the waste's characteristics and to the distribution of water in the material. The sensitivity of TDR was quantified relative to MSW composition and density, the initial θ and θ distribution, the electrical conductivity (EC) of the fluid, and the rate of change in θ. Experiments were conducted on two different waste materials and on a sand–gravel mixture in a small-scale laboratory cell. The relationship between TDR measurement and true θ was calibrated for all experiments. The effect of waste composition and density appeared to be minor compared with the effect of the initial θ and the θ distribution around the probes. This research opens a way for an effective use of TDR in large-scale experiments with MSW.