Little is known about the agronomic aspects of Mexican Sunflower (Tithonia diversifolia), in spite of its potential for multiple uses. In this study, we evaluated the effects of application rates of biofertilizer and irrigation on yield, growth, and leaf chlorophyll and nutrient content of Mexican Sunflower. In an experiment in the Brazilian semi-arid region, we used a 5 × 2 factorial arrangement, consisting of five application rates of biofertilizer (0, 40, 80, 120, and 160 m3 ha-1), with and without irrigation. The statistical design was randomized blocks with three replications. Irrigated plants of Mexican Sunflower had greater dry and fresh matter yields, greater height, and greater leaf area index and leaf contents of K, Zn, and B. However, the high concentration of bicarbonate in the irrigation water reduced the leaf contents of N, Ca, S, Fe, and Mn. The mean increase in the two cuttings obtained with the use of irrigation was 350% and 314% for fresh and dry matter, respectively. The increase in the biofertilizer application increased the leaf chlorophyll contents of irrigated plants; however, it did not result in production or nutritional gains. In regions with low availability of rainfall, irrigated cultivation of Mexican Sunflower is recommended.