A simple, sensitive, and selective solid phase extraction—ultra-fast liquid chromatography—tandem mass spectrometry (SPE-UFLC-MS/MS) method was developed and applied for the analysis of selected important pharmaceutical compounds in source and finished drinking waters. The method detected the following six pharmaceuticals, cotinine, cephapirin, ciprofloxacin, enrofloxacein, azithromycin, and diphenhydramine, at sub-µg/L level in multiple water matrices after pre-concentration by SPE. Cotinine-d3 and 13C315 N-Ciprofloxacin were used as internal standards for accurate quantitation. This method was validated through spike recoveries (67-129%), reproducibility (RSD: 2.3-15.7%), and method detection limits (MDLs: 2-5 ng/L). The method was used to test for occurrence of these pharmaceuticals in source and drinking waters from 13 Missouri water treatment facilities in four different seasons. In general, higher detection frequency and concentrations of pharmaceuticals were observed in colder months due presumably to less dilution (at lower flows) and slower degradation. The PPCP removals by different activated carbons were also evaluated. The occurrence and removal results in this study provide valuable information to help water treatment facilities taking appropriate strategies for better control of trace pharmaceuticals in drinking water.