Irrigation and fertilization play key roles in crop production. Scarcity of available water resources and low nutrient use efficiency calls for a need to improve water and nitrogen (N) use efficiency. This study aimed to investigate the effects of different irrigation and nitrogen treatments on the growth, yield, irrigation water-use efficiency (IWUE) and fertilizer-N utilization of tomato plants by using pre-buried soil columns (100 cm in depth) in a field. The irrigation treatments included conventional drip irrigation (CDI) and alternate partial root-zone drip irrigation (ADI) with sufficient or deficient water supply. Nitrogen fertilizer was set as high and low N input (8.30 g or 4.15 g 15N-labeled urea per plant) supplied as drip fertigation. Compared with the CDI treatment at the same nitrogen drip fertigation level, ADI promoted tomato root growth, induced more 15N accumulation in the 0−100 cm soil profile, facilitated the absorption of fertilizer-15N as well as soil N by plants, thus increasing plant growth and yield as well as IWUE and fertilizer-N use efficiency, while decreased 15N loss. Low nitrogen supply decreased plant growth, yield, 15N absorption, 15N accumulation in soil profile and IWUE, but increased both the 15N-use efficiency and 15N loss percentage. Thus, ADI coupled with nitrogen fertigation has a potential to save irrigation water, increase use efficiencies of both water and nitrogen fertilizers with reduced loss of N to the environment.