Globe artichoke is propagated by seed (seed propagated, SP) or by plant (vegetative propagated, VP). To date, there is a lack of knowledge of how the propagation system affects the life cycle resource use and environmental performance of globe artichoke production. We combined energetic, exergetic, and environmental life cycle assessment (LCA) to explore “cradle-to-farm gate” resource use and environmental impacts of Mediterranean globe artichoke production using VP and SP. The cumulative energy and exergy were calculated using cumulative energy demand (CED) and cumulative exergy extraction from the natural environment (CEENE). The environmental impacts classified in different impact categories were assessed using the ReCiPe 2016 method. The functional units were 1 ton of artichoke heads (reflecting production efficiency) and 1 ha of cropped land (reflecting production intensity). The results show that the VP globe artichoke generate 14% lower CED (64,212 vs. 75,212 MJ ha−1) and 17% lower CEENE (88,698 vs. 106,664 MJexha−1) per 1 ha of land while 1 ton of product generates higher impact: 29% CED (5384.4 MJ vs. 4178.5 MJ ton−1) and 25% CEENE (7391.5 vs. 5927 MJex ton−1). On a mass basis, SP artichokes had lower water consumption (−18%), freshwater and marine ecotoxicity (−47%), and stratospheric ozone depletion (−32%), but a higher global warming (+19%), fossil (+36%) and mineral scarcity (+39%), and human toxicity-related impacts (+27%). At the endpoint level, VP globe artichoke has higher damage to human health (+13.4%) and ecosystem quality (+20.5%), but lower to resource availability (−24.5%). The single-score LCA analysis indicated that SP globe artichokes generate a 24% higher impact per 1 ha (1911.3 vs. 1452.7 points) but 14% less per unit of product (106 vs. 121.1 points). For both systems, water and fertilizer should be used more carefully and efficiently since the application of irrigation, fuel, and fertilizers were the major contributors to total environmental damage.