Accurate determination of emerging contaminants in drinking water constitutes a major environmental challenge for which highly sensitive analytical methods are needed. This work details the development of a novel highly sensitive solid-phase extraction-high performance liquid chromatography-tandem mass spectrometry (SPE-HPLC-MS/MS) method for simultaneous determination of a diverse panel of widely used trace contaminants, including two pharmaceuticals (fluoxetine and gemfibrozil), three pesticides (3-hydroxycarbofuran, azinphos-methyl, and chlorpyrifos), and two hormones (testosterone and progesterone) in water. The method is highly reproducible and sensitive with detection limits at subnanogram per liter level (0.05—0.5Â ng/L). It was used to monitor the occurrence of these contaminants in source and drinking water across 18 drinking water treatment facilities in Missouri, USA in 1Â year including cold winter and hot summer seasons. The experiment results indicated that all of the monitored contaminant concentrations are very low, lower than or close to the method detection limits, in the selected water treatment facilities. Pesticide concentrations were slightly elevated in some source waters during hot season, whereas slightly higher pharmaceuticals were observed during cold season. The concentrations of two hormones were lower than the limits of detection in all the water samples. These contaminants were present, if any, at below detection limits in all treated drinking water samples analyzed, suggesting that treatment processes effectively removed the contaminants studied herein.