The study of the Moho beneath thick sedimentary basins involving natural earthquakes is challenging, as low‐velocity materials often cause strong reverberations that mask Moho signals. Here, we develop a method to determine the depth of the Moho by taking advantage of the presence of the sediments. The method utilizes the first Pn crustal multiple from regional earthquakes PnPn and its differential travel time with respect to Pn. PnPn is usually weak in amplitude; thus, it is difficult to identify in regions without a sedimentary cover. However, PnPn is significantly amplified in the presence of low‐velocity sediments because of an increase in the near‐surface P‐to‐P reflection coefficient. The arrival time, amplitude, and wave shape of PnPn, if normalized by the reference Pn, are insensitive to earthquake source parameters, such as focal mechanism and focal depth. We demonstrate the potential of this method using both 1D and 2D waveform simulations. Synthetic waveforms suggest that PmpPn and PnPmp (one Pn leg merges to PmP near the source or the receiver) largely contribute to the PnPn amplitudes, which depend on the near‐surface structure at their free‐surface P‐to‐P reflection points. We further validate the method with two field examples in the Imperial Valley; one is near the United States–Mexico border, and the other is in Oklahoma in the central United States. Both examples suggest that the method can be used to study the Moho either near the source or the receiver.