The largest wastewater treatment plant in Jordan was monitored in the summer to determine the removal of pharmaceuticals and personal care products (PPCPs). Grab samples were collected from the influent and effluent of As-Samra Wastewater Treatment Plant (WWTP). Liquid chromatography and tandem mass spectrometry (LC–MS/MS) were utilized to determine the concentrations of 18 compounds of pharmaceuticals and personal care products (PPCPs). The results showed that 14 compounds were detected in the collected samples from the influent and effluent of As-Samra WWTP. These compounds are 1,7-dimethylxanthine, amphetamine, acetaminophen, caffeine, carbamazepine, cimetidine, cotinine, diphenhydramine, methylenedioxymethamphetamine (MDMA), morphine, phenazone, sulfamethazine, sulfamethoxazole, thiabendazole, and trimethoprim. However, four compounds were below the detection limit (<0.005 µg/L), namely cimetidine, methylenedioxyamphetamine (MDA), methamphetamine, and sulfachloropyridazine. Among PPCPs, the highest estimated average concentrations in raw wastewater were caffeine, acetaminophen, 1,7-dimethylxanthine, cotinine, and carbamazepine sampled during the summer, at an estimated concentration of 155.6 µg/L, 36.7 µg/L, 10.49 µg/L, and 1.104 µg/L, respectively. However, the highest estimated average concentrations in treated wastewater were for carbamazepine, sulfamethoxazole, caffeine, cotinine, and acetaminophen, at 0.856 µg/L, 0.096 µg/L, 0.086 µg/L, 0.078 µg/L, and 0.041 µg/L, respectively. In general, the results showed that some compounds in the collected samples of wastewater in Jordan have concentrations exceeding the values reported in the literature. The removal efficiency rates of 1,7-dimethylxanthine, acetaminophen, caffeine, cotinine, morphine, and trimethoprim were higher than 95%, while those of carbamazepine, sulfamethazine, and sulfamethoxazole were lower than 22.5%. Moreover, diphenhydramine and thiabendazole had negative removal efficiency rates. The removal efficiency rates of the PPCPs in As-Samra WWTP were generally consistent with those of indicator compounds reported in the literature for conventional WWTPs.