Viticulture is of great economic importance in the southern part of Bosnia and Herzegovina, thanks to favorable climatic conditions and a long-standing tradition of growing vines. The assortment is dominated by international varieties, as well as some autochthonous and domesticated varieties. The subject of the research is the analysis of the quality of Cabernet Sauvignon, Merlot, Vranac, and Blatina varieties at two localities in Herzegovina during the period 2020–2021. The paper examined the most important economic and technological characteristics, grape quality, and berry phenolic profile. A particularly pronounced variation of the tested characteristics during the research period was observed in the Merlot and Blatina varieties, while the Cabernet Sauvignon and Vranac varieties showed a slightly higher stability of the tested characteristics. Poorer grape quality during the research period was registered with the Blatina variety, which can be considered a varietal characteristic to some extent. The analyzed grape varieties were rich in polyphenols, and the impact of grape variety on the berry phenolic profiles was confirmed. The most abundant polyphenols in the analyzed grape samples were quercetin 3-O-glucoside and catechin gallate, followed by kaempferol 3-O-glucoside. The highest values of polyphenols were found mainly in the samples originating from Trebinje. Indigenous Balkan grape varieties (Vranac and Blatina) stood out with particularly high contents of some phenolics. Research has shown that climatic conditions have a significant influence on the most important characteristics of grapes, which are conditioned by genotypic specificities. The conditions for growing vines in the conditions of Herzegovina enable high quality in the production of grapes, especially the Cabernet Sauvignon and Vranac varieties. The autochthonous variety Blatina shows significant variations in grape quality during the test period, which was confirmed by the results of a larger number of studies in the previous period.