Density variation during the injection molding process directly reflects the state of plastic melt and contains valuable information for process monitoring and optimization. Therefore, in-situ density measurement is of great interest and has significant application value. The existing methods, such as pressure−volume−temperature (PVT) method, have the shortages of time-delay and high cost of sensors. This study is the first to propose an in-situ density measurement method using ultrasonic technology. The analyses of the time-domain and frequency-domain signals are combined in the proposed method. The ultrasonic velocity is obtained from the time-domain signals, and the acoustic impedance is computed through a full-spectral analysis of the frequency-domain signals. Experiments with different process conditions are conducted, including different melt temperature, injection speed, material, and mold structure. Results show that the proposed method has good agreement with the PVT method. The proposed method has the advantages of in-situ measurement, non-destructive, high accuracy, low cost, and is of great application value for the injection molding industry.