Morinda officinalis (Rubiaceae) is a traditional Chinese medicine widely used for the treatment of impotence and osteoporosis in clinical therapy. In the present study, a rapid and simple ultra-high performance liquid chromatography with photodiode array detection method was developed and validated for the simultaneous determination of 11 bioactive compounds in M. officinalis. This assay method was validated with respect to linearity (R > 0.9991), precision, repeatability, limit of detection, limit of quantification, and accuracy (with observed recovery rates between 94.21 and 100.38%). The quantitative results revealed significant differences in the concentrations of the selected compounds. Additionally, chemometric methods, including hierarchical clustering analysis, principal component analysis, and partial least-squares discriminate analysis, were applied to compare and sort the 25 batches of M. officinalis samples based on the quantitative data of the analytes. All of the samples were clearly divided into two groups: the Hainan samples were successfully discriminated from the samples from other origins. Simultaneous determination of multiple compounds using the proposed method combined with chemometrics could be a viable strategy to compare and evaluate the quality of M. officinalis.