Dual-energy X-ray imaging can provide material-specific image information, which is very useful in inspection tasks. Accurate and efficient material decomposition is desirable in such tasks, and we developed a fast and efficient dual-energy calibration method for high-energy X-ray cargo inspection. We designed a calibration phantom consisting of a half cylinder of lead and a half cylinder of carbon. We used a least-squares method to determine the material decomposition formula from the calibration-phantom data. To test the feasibility of the proposed method, we designed a cargo phantom in a simulation study. Material decomposition was successfully conducted, so we expect the proposed calibration method to play an important role in high-energy X-ray imaging for cargo inspection.