The present work was carried out to evaluate the effects of irrigation with two different municipal wastewaters (secondary-treated wastewater (SW) and tertiary-treated wastewater (TW)) compared to freshwater (FW) on main qualitative parameters of three different classes of globe artichoke (main, secondary, and processing heads). The experimental trial was conducted in Southern Italy (Apulia region) for two cropping cycles (GS1 and GS2) using ‘Violetto di Provenza’ as cultivar. The artichoke heads were analyzed for proximate composition (dry matter, total sugar, total fat, ash, and total protein), percentage of edible part, mineral profile (sodium, potassium, magnesium, calcium, copper, iron, nickel, zinc, chloride, nitrate, phosphate, and sulphate) and polyphenolic acids content (caffeoylquinic acids and flavones). Both SW and TW treatments caused an increase of the percentage of the edible part, head protein contents, and mineral elements of the main and processing heads. Moreover, SW statistically increased the caffeoylquinic acid derivatives and the trans-ferulic acid content, while both SW and TW the flavones content. Finally, according to the multivariate analysis adopted, in our experimental conditions, the mineral component of the heads, such as chloride, potassium, copper, and zinc content, had a greater weight in the separation of FW, SW, and TW. On the other hand, the polyphenolic 5-O-caffeoylquinic acid, trans-ferulic acid, and 1,5-di-O-caffeoylquinic acid had a greater weight in the separation of the head class groups (main, secondary, and processing). Moreover, the trans-ferulic acid content of the heads was related both to the irrigation water type and to the different head classes.