Hemp (Cannabis sativa L.) has a low impact on the environment requiring few added resources, and has multiple downstream applications. There is little information on hemp biomass, seed yields, and response to NPK fertilization under humid rainfed Mediterranean conditions. Moreover, the effects of hemp on subsequent wheat (Triticum aestivum L.) crops have not been determined. To address these issues, we performed a field study for 6 yr in Catalonia (northeastern Spain). Hemp treatments included: hemp monoculture, unfertilized hemp succeeding wheat, and NPK-fertilized hemp succeeding wheat. In turn, wheat treatments included: wheat monoculture, first-, second-, and third-year wheat succeeding unfertilized hemp, and first-, second-, and third-year wheat succeeding NPK-fertilized hemp. The hemp biomass yields (5340–10,090 kg ha–1) were similar to or lower than those achieved in other European regions whereas the hemp seed yields were relatively high (604–1434 kg ha–1). Both the biomass yield and seed yield greatly increased with NPK fertilization. The rotation effects of hemp on the subsequent wheat crops increased the wheat yield by 1368 and 155 kg ha–1 in the first and second years, respectively, but in the third year the yield was similar to the wheat monoculture. The beneficial effects of hemp on wheat therefore appear to last for 2 yr. We conclude that dual-purpose hemp (harvested for fiber and seed) is an excellent predecessor for wheat, improving the sustainability of cereal-based cropping systems under humid rainfed Mediterranean conditions.