Active substances detected in surface water in Hungary today include pain and anti-inflammatory agents and antiepileptics, as wastewater treatment mechanisms cannot remove these micropollutants. The aim of our research is to detect residues of four pain-killer drugs—naproxen, nimesulide, diclofenac, and ibuprofen—and an anti-epileptic drug—carbamazepine—in water samples we collected (n = 8) from the Danube. Our samples were concentrated using solid-phase extraction and then detected with HPLC. During the evaluation, we looked for a significant difference in the concentration of the active substances. Naproxen was detectable in the largest amount in one sampling point, with an average concentration of 12,029.337 ± 1772.957 ng/L, while ibuprofen was present in the second highest concentration in another sampling site, which reached an average concentration of 4048.112 ± 2086.789 ng/L. We examined water samples taken from the same sampling sites but at different distances from the riverbank, and we found a significant difference regarding the active substance naproxen at the sampling site in Budapest District XX. The analytes were detected in varying amounts in all the water samples, so the contamination in the examined section is significant. Examining the turnover data on medicines and our results, we concluded that pharmaceutical consumption significantly contributes to the pollution of the Danube. In order to protect water quality, further research would be advisable in the field of mechanisms for wastewater treatment in order to achieve the complete removal of drug residues from wastewater.