Aims: To study the effect of different irrigation and fertigation levels as well as their Indeterminate on soil fertility, nutrient uptake, and fruit yield of watermelon. Study Design:  Strip-plot design. Place and Duration of Study: A field experiment was conducted at the Department of Vegetable Science, Dr. Panjabrao Deshmukh Krishi Vidyapeeth, Akola during the summer season 2018-19 and 2019- 2020. Methodology: Two factors of irrigation and fertigation and three levels in each factor and the nine combinations of irrigation and fertigation levels were evaluated against the soil fertility, nutrient uptake, and fruit yield of watermelon. Results: The results revealed that the soil pH was reduced while the organic carbon content increased with an increase in fertigation levels. In general, pooled mean revealed that available nitrogen (N), phosphorus (P), and potassium (K) were higher by 4.8, 16.9, and 4.5%, respectively, in F1 (125% RDF through fertigation) over F3 (75% RDF through fertigation) and significantly maximum availability was observed under the treatment combination of I2F1. The uptake of N, P, and K under I1 (100% of irrigation water requirement (IWR)) and F1 were increased by about 12 and 22, 27 and 21, and 32 and 31% over that of irrigation level I3 (60% IWR) and fertigation level F3, respectively. The pooled data of fruit yield revealed that the I2 (80% IWR) irrigation level and F1 fertigation level had 35.39 and 36% higher fruit yield of watermelon as compared to I3 and F3, respectively. Among the different irrigation and fertigation levels, a significantly maximum fruit yield of watermelon was observed under I2F1, followed by I2F2. Conclusion: The study demonstrated the superiority of combining irrigation and fertigation combination of I2F1 for improving soil fertility and watermelon yield, potentially saving up to 20% of irrigation water.