In practical implementations, most nuclear reactors employ digital controllers to accomplish the load following operation. However, most of the pre-existing works only focus on continuous time controller design, which may yield degraded control performance when the control strategy is employed by a digital controller owing to the finite sampling frequency and the inevitable discrete-time approximations. To this end, this paper proposes a discrete-time sliding mode prescribed performance controller (DTSMPPC) via Kalman filter (KF) and disturbance observer (DO) for a pressurized water reactor (PWR), aiming to achieve an easier implementation on the practical nuclear reactor systems. Specifically, the continuous mathematical model of the PWR system with consideration of model errors and disturbances is first transformed to a discrete-time form by virtue of Euler’s discretization technique. Then, based on this transformed discrete-time model, the KF and DO, which provide the estimates of unmeasured system states (relative density of delayed neutron precursor, average fuel temperature, xenon concentration, and iodine concentration) and uncertainties, respectively, are constructed using the input/output measurement information acquired from the nuclear reactor system merely. By incorporating the observed information provided by the KF and DO into the control framework, the proposed DTSMPPC enables the load following error to fulfill the accurate and robust performance requirement even in the presence of unmeasured system states and uncertainties, while at the same time ensuring the transient and steady-state load following error within a prescribed zone described by performance functions. The system stability and the aforementioned theoretical findings are proved through rigorous analysis and simulations. Simulation results also reveal that the proposed DTSMPPC via the KF and DO yields a superior load following performance compared with some previous control strategies.