This work presents a detector‐integrated two‐tier control architecture capable of identifying the presence of various types of cyber‐attacks, and ensuring closed‐loop system stability upon detection of the cyber‐attacks. Working with a general class of nonlinear systems, an upper‐tier Lyapunov‐based Model Predictive Controller (LMPC), using networked sensor measurements to improve closed‐loop performance, is coupled with lower‐tier cyber‐secure explicit feedback controllers to drive a nonlinear multivariable process to its steady state. Although the networked sensor measurements may be vulnerable to cyber‐attacks, the two‐tier control architecture ensures that the process will stay immune to destabilizing malicious cyber‐attacks. Data‐based attack detectors are developed using sensor measurements via machine‐learning methods, namely artificial neural networks (ANN), under nominal and noisy operating conditions, and applied online to a simulated reactor‐reactor‐separator process. Simulation results demonstrate the effectiveness of these detection algorithms in detecting and distinguishing between multiple classes of intelligent cyber‐attacks. Upon successful detection of cyber‐attacks, the two‐tier control architecture allows convenient reconfiguration of the control system to stabilize the process to its operating steady state.