The present work describes the application of an analytical procedure, utilizing ultra performance liquid chromatography (UPLC) coupled with mass spectrometry instrumentation, for the determination of 253 multiclass pesticides, classified in six different groups. Solid phase extraction was applied for the isolation and pre-concentration of target compounds in water samples. Surface waters of the lakes located in Northern Greece (Volvi, Doirani, and Kerkini), were collected in two time periods (fall/winter 2010 and spring/summer 2011) and analyzed, applying the developed analytical methods. Spatial distribution of detected pesticides was visualized using interpolation methods and geographical information systems (GIS). Pesticides with maximum concentrations were amitrole, propoxur, simazine, chlorpyrifos, carbendazim, triazophos, disulfoton-sulfone, pyridaben, sebuthylazine, terbuthylazine, atrazine, atrazine-desethyl, bensulfuron-methyl, metobromuron, metribuzin, rotenone, pyriproxyfen, and rimsulfuron. In Lake Kerkini, mainly carbamates and triazines were determined at elevated concentrations, near the coastal point of the NW side of the lake. Seasonal variations were strong among the applied pesticide classes and determined concentrations, indicating the contribution of pesticide application patterns and rainfall. Lake Doirani exhibited organophosphate pesticides at higher concentrations mainly at coastal points, while triazines emerged as the main pollutant during spring sampling. Lake Volvi exhibited the highest pesticide concentrations, mostly triazines and ureas at the central part of the lake. The occurrence of extreme values and nonconstant seasonal variations indicated that the concentrations were increased disproportionately during the second sampling, as a result of the varying contribution of pollution sources right after the application period. In all cases, the total concentration of pesticides increased during the second sampling period.