<p>The slab thickness is becoming increasingly larger to meet the thick plate requirement in marine, construction and energy industries. The secondary cooling process in ultra-thick slab continuous casting involves multi-phases and multi-physical fields, which is crucial for optimizing slab solidification and preventing defects. In this study, both nozzle spray and secondary cooling models have been developed and validated to analyze and optimize spray cooling behavior in an ultra-thick (460 mm) slab continuous caster. The simulated results demonstrate the transformation of high-pressure water jets into fine droplets. Variations in water flow rate significantly influence spray angles, recorded at 88.84 deg for 1.58 L/min, 91.69 deg for 2.48 L/min, and 98.58 deg for 4.14 L/min, which enhance gas–liquid interface instability and promote atomization. Increased water flow rates markedly intensify slab surface cooling. Wider droplet dispersion is observed at higher spraying distances, though droplet concentration tends to decrease. Slower casting speed extends spray–slab contact time, further enhancing cooling effects under the same water flow rate. Additionally, a multiple linear regression model was fitted to assess heat transfer coefficients at the foot roller zone. Despite achieving the required metallurgical reheat rate (≤ 100 °C/m), slab corner temperatures in the straightening zone remain within temperature range of the third brittle zone (671 °C to 705 °C), leading to potential crack formation. The secondary water flow rate was optimized to improve temperature distribution uniformity across the slab; the transverse temperature differences were reduced by an average of 30.6 °C to avoid the third brittle zone, for the purpose of minimizing crack risk.</p>