Basil is an important aromatic plant largely used in medicine and for the preparation of traditional dishes in the Mediterranean area. The purpose of this work was to compare two closed soilless cultivation systems—aeroponics and a pot system—in terms of the quality, shelf-life and yield of the sweet basil (Ocimum basilicum L.) they produced, which is grown in an all-year-round production site in Pisa, Tuscany (Italy). The content of total chlorophylls, carotenoids, total phenols, antioxidant capacity, and rosmarinic acid content, as well as a post-harvest storage analysis, were investigated in fresh-cut sweet basil from both cultivation systems. Numerous postharvest tests have been carried out during each season (spring, summer, autumn, winter), evaluating the quality of the basil after its packaging and storage in a fridge at about 6-8°C in the dark on different days after harvest (3, 6 and 9 days), simulating the normal commercial cycle of fresh-cut sweet basil in supermarkets. Our study showed that sweet basil plants cultivated in aeroponics produced almost double the yield for the same area, with a better water use efficiency (WUE), and had a higher shelf-life in comparison with basil grown in pots in the same periods and with the same climatic conditions. Tests of post-harvest production in sweet basil have shown that the quality obtained by the aeroponic system was similar or sometimes higher compared to that of pot cultivation. Nitrates, on the other hand, tended to be higher in the pots cultivated in spring; however, the values ​​were lower than the maximum limits indicated by the European Food Safety Authority (EFSA). The aeroponic cultivation system tested provided a good qualitative–quantitative production of sweet basil across the four seasons. The aeroponic system, like all closed soilless cultivation systems, has the advantage of increasing production compared to cultivation in a substrate, with a higher water and fertiliser use efficiency and the advantage of not producing exhausted substrate at the end of the cultivation cycle.