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Providing the world's population with sufficient and nutritious food through sustainable food systems is a major challenge of the twenty-first century. Fertilizer use is a major driver of crop yield, but a comprehensive synthesis of the effect of fertilizer on the nutritional quality of food crops is lacking. Here we performed a comprehensive global meta-analysis using 7859 data pairs from 551 field experiment-based articles published between 1972 and 2022, assessing the contribution of fertilization with a wide set of plant nutrients to the nutritional quality of food crops (i.e., fruits, vegetables, cereals, pulses/oil crops, and sugar crops). On average, fertilizer application improved crop yield by 30.9% (CI: 28.2–33.7%) and nutritional quality (referring to all nutritionally relevant components assessed; carbohydrates, proteins, oil, vitamin C, representative mineral nutrients, and total soluble solids) by 11.9% (CI: 10.7–12.1%). The improvements were largely nutrient- and crop species dependent, with vegetables being the most responsive. Potassium, magnesium, and micronutrients played important roles in promoting crop nutritional quality, whereas the combined application of inorganic and organic source(s) had the greatest impact on quality. Desirable climatic conditions and soil properties (i.e., silt loam, soil organic matter 2.5–5.0%, and pH 4.5–8.5) supported further enhancements. Considering cross-continent responsiveness, the increase in the nutritional quality of food crops with fertilizer application was greatest in Africa. In a nutshell, our findings pave the way towards a quantitative understanding of nutrient management programs and responsible plant nutrition solutions that foster the sustainable production of nutritious and healthy food crops for human consumption. [ABSTRACT FROM AUTHOR]