In recent decades, one of the biggest challenges facing agriculture has been sustainability. To achieve sustainability goals, it is necessary to consider the compatibility of environmental, economic, and energy aspects. The main aim of this study is to conduct an environmental-economic-exergy assessment of safflower production under different tillage systems with Zn and Fe micronutrients using life cycle cost (LCC), life cycle assessment (LCA), and exergoeconomic analysis. For this purpose, three scenarios are evaluated: conventional tillage (Sc-CT), reduced tillage (Sc-RT), and no-tillage setup (Sc-NT). The LCA method ReCiPe2016 is used to assess environmental impacts based on one ton of safflower seeds as a functional unit. In addition, the emissions social cost (ESC) is considered as a hidden part of LCC in safflower production. Finally, a combination of cumulative exergy demand and net profit is used to compute an exergoeconomic index in agriculture as a novelty. Results indicate that On-Farm emissions derived from nitrogen and diesel fuel are the most significant contributor, accounting for over 50% of the impact on human health and ecosystems. Sc-RT with 62.62 Pt and Sc-NT with 71.66 Pt are the best and worst LCA scenarios of this study. Sc-CT has the highest ESC, with 51.14 $, and Sc-NT has the lowest LCC, with 380.39 $. Exergy results show that nitrogen fertilizer has the largest share of cumulative exergy demand, and Sc-RT, with 0.073 $ MJ−1, is the best scenario from an exergoeconomic perspective. In summary, Sc-RT, Sc-CT, and Sc-NT are ranked first, second, and third, respectively, from an environmental-economic-exergy-friendly point of view.