A high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (LC/ESI-MS) method under selected ion monitoring mode (SIM) was developed to quantitate the predominant catechins, catechin, epicatechin, epicatechin-3-O-gallate, and epigallocatechin-3-O-gallate, in the medicinal plant catechu (Acacia catechu). Other major secondary products including caffeine, flavanol dimers, and flavonol glycosides were also identified by their molecular ion peaks and fragmentation peaks using LC/MS and LC/MS/MS. For the investigated ion concentration ranges of catechin, epicatechin, epicatechin-3-O-gallate, and epigallocatechin-3-O-gallate, good linearities (r2 > 0.99) were obtained for each calibration curve. Validation for this method showed an accuracy ranging from 1.06 to 11.76%, and the precision (relative standard deviation) varied between 1.60 and 9.36% for these four analytes. This is the first quantitative determination of all predominant catechins in catechu heartwood and leaves.