Accumulation of high level of nitrate (NO3−) in leaves is a serious issue for vegetable crops like lettuce (Lactuca sativa L.). Therefore, this study aimed to limit NO3− level by adjusting the balance between fertilization and irrigation program in lettuce. In a strip plot design with three replicates, lettuce plants were grown under four fertilizer treatments and three irrigation regimes. Three organic fertilizers (biochar, compost and vermicompost), in addition to mineral fertilizer, were used. The irrigation regimes were 60, 80 and 100% of crop evapotranspiration, ETc (ETc60, ETc80, and ETc100). Nitrogen (N), phosphorus (P) potassium (K) and organic matter (OM) in soil as well as yield, N, P, K and NO3− of lettuce were estimated. Findings showed that vermicompost or biochar (with any irrigation regime) as well as compost with irrigation by ETc60 were the effective combinations for increasing K content in soil after harvest. Under irrigation by ETc80 or ETc100, vermicompost or biochar were the efficient treatments for increasing lettuce yield equaling the farmer common practice (ETc100 x mineral fertilizer). Under irrigation by ETc60, mineral fertilizer or vermicompost showed the highest lettuce leaf content of K. Moreover, ETc60 or ETc80 x mineral fertilizer recorded the maximum NO3− content of lettuce leaves. The accumulation of nitrate in lettuce leaves owing to mineral fertilizer reached about 1.24 times than that of organic fertilizers. Compost x ETc80 or ETc100 showed the minimal NO3–N accumulation, hence, high relative reductions in NO3–N accumulation as compared to the common practice (ETc100 x mineral fertilizer) were observed. In conclusion, irrigation by 80% instead of 100% of crop evapotranspiration of organically fertilized lettuce (especially with vermicompost) could be adopted since such practice recorded high lettuce productivity with low NO3− content.