The signal processing technique is one of the principal tools for diagnosing power quality (PQ) issues in electrical power systems. The Discrete Fourier Transform (DFT) is a frequency analysis technique used to process power system signals and identify PQ problems. However, the DFT algorithm may lead to spectral leakage and picket-fence effect problems for asynchronously sampled signals that contain harmonic, inter-harmonic, and flicker components. To resolve this shortcoming, a hybrid method for frequency estimation based on a second-level DFT approach and a frequency-domain interpolation algorithm to obtain the accurate fundamental frequency of a power system is proposed in this paper. This method uses a second-level DFT to compute the cosine and sine parts for the fundamental frequency components of the acquired signals. Then, a frequency-domain interpolation approach is adopted to determine the amplitude ratio for the cosine and sine parts of the system’s fundamental frequency. A set of mixed signals with harmonic, inter-harmonic, and flicker components with the fundamental frequency deviation is used. The evaluation results demonstrate the superiority of the new method over other approaches for assessing asynchronously sampled signals contaminated with noise, harmonic, inter-harmonic, and flicker components.