Licorice extract powder, the aqueous extract of licorice, has been widely used as a common raw material in both pharmaceutical and food fields. Its quality evaluation is of great significance but still a big challenge due to complex chemical components. In this study, a rapid and efficient HPLC-DAD method for fingerprint profiling and multiple components determination was developed and validated to assess the quality consistency of licorice extract powder. The chromatographic fingerprints at five wavelengths were fused into a synthesized fingerprint to avoid one-sidedness of single wavelength. Then, quality grades of 72 batches of licorice extract powders from different manufacturers were successfully discriminated by geometric linear quantified fingerprint method, in which both qualitative and quantitative evaluation parameters were obtained. Principle component analysis revealed that samples from different manufacturers can be clustered according to the contents of six main components, same as the fingerprint evaluation results. Furthermore, the fingerprint-efficacy relationship among the components as well as the antioxidant activity in vitro was investigated by partial least squares model, which offered significant medicinal efficacy information. The present study established a powerful and reliable method to monitor the quality consistency of licorice extract powder.