Evaporative cooling with spray and fan is one of the most common and efficient approaches to alleviate the heat stress of cows in summer. Previous studies have showed spray-fan systems can be used to reduce the respiration rate, body temperature, and culling rate, while increasing milk productivity. However, the use of the spary-fan cooling system can be costly in terms of water and electricity, and it generates a large amount of wastewater. An ideal cooling system is required to enhance the thermal comfort while minimizing the resource cost. Specifically, the spray direction from perpendicular to parallel relative to the cow’s body can be expected to reduce water consumption for the potentially promising cooling. Additionally, the spray frequency is the key influencing factor on the balance between cooling effectiveness and water efficiency. In this study, a systematic evaluation was conducted on the impact of different spray directions and frequencies on the cows’ physiological responses (rectal temperature and respiration rate). The optimal strategy was also determined to balance the cooling effect and water efficiency. A total of 20 Holstein cows were randomly assigned to five treatments: no spray; spray perpendicularly for 40 s on and 300 s off (8 cycles); spray parallelly for 40 s on and 300 s off (8 cycles); spray parallelly for 20 s on and 320 s off (8 cycles); as well as spray parallelly for 40 s on and 640 s off (4 cycles). Each group of cows was evaluated between 11:00 and 12:30 or between 14:00 and 15:30 in the test period. Each cow was measured at the same time in the trial. Five treatments were conducted daily over the two time periods. Each treatment was replicated three times per cow over a total of 15 days. The order in which treatment was received by each cow was balanced and randomized. Results showed that the baseline rectal temperature and respiration rate affected the magnitude of the changes, with cows exhibiting a greater reduction when their initial respiration rate and rectal temperature values were higher. The parallel spray direction with a spray frequency of 40 s on and 300 s off resulted in the greatest reductions in rectal temperature (0.55 to 0.62 ℃ lower than the baseline value) and respiration rate (12 to 20 breaths/min lower than the baseline value). Spraying cows in a parallel direction and shortening the spray-on duration from 40 to 20 s (spray-off duration was 320 s) resulted in similar reductions in the rectal temperature and respiration rate as the parallel spray direction with a 40 s spray-on duration (spray-off duration was 300 s), over most measurement period. In addition, the spraying cows with a shorter spray-on duration consumed less spray water (50 percentage points lower). In conclusion, a more effective spray strategy was to spary cows in parallel in the smart and precision cooling systems. In practice, the optimal spray strategy can be determined by balancing the cooling effect and water efficiency, according to the specific on-site conditions.