This study aimed to determine the effect of irrigation amount and irrigation frequency on drip-irrigated flue-cured tobacco evapotranspiration (ETa), yield, and water use efficiency. Four irrigation treatment levels were imposed: 100% IRT (fully irrigated treatment, no stress), 85% IRT, 70% IRT, RFT (rainfed treatment), and high, medium, and low irrigation frequencies were set. The relationship between irrigation volume and yield is a quadratic curve. The evapotranspiration had a positive relationship with the irrigation amount. The yield of flue-cured tobacco was the highest in 2016 (wet year), and the corresponding ETa was the smallest. The irrigation water use efficiency (IWUE) in the driest year, 2017, was lower than IWUE in the wet years 2015 and 2016, and the crop water use efficiency (CWUE) had similar results for the three years. IWUE increased with irrigation amount. The effect of irrigation frequency on CWUE was not significant. The CWUE had a positive relationship with yield. No significant differences due to irrigation frequency were found for yield.