Cardoon seeds have been proved to thrive in the Mediterranean region, even under low input management and its biomass is suitable for several food and industrial uses. Despite that, a proper value chain has not been set properly and uncertainty still lays among producers and industries, particularly concerning the harvesting stage. The present study supports, via field trials, the hypothesis that cardoon seeds can be harvested using a conventional combine harvester equipped with the sunflower header. Theoretical field capacity (TFC), effective field capacity (EFC), and field efficiency (FE) were 2.36 ha h⁻¹, 2.05 ha h⁻¹, and 1.82 Mg h⁻¹, respectively, while harvesting costs were calculated as 69.52 € ha⁻¹. Seed loss was only 3.2% w/w of the potential seed yield. The machinery’s performance, costs, and seed loss are comparable with sunflower harvesting, underlying the possibility to use the available technology directly to harvest cardoon seeds.