This study attempts to develop a real-time debonding monitoring system for carbon fiber-reinforced polymer (CFRP) strengthened structures by continuously inspecting the bonding condition between the CFRP layer and the host structure. The uniqueness of this study is in developing a new concept and theoretical framework of nondestructive testing (NDT), in which debonding is detected without relying on previously-obtained baseline data. The proposed reference-free damage diagnosis is achieved based on the concept of time reversal acoustics (TRA). In TRA, an input signal at an excitation point can be reconstructed if the response signal measured at another point is reemitted to the original excitation point after being reversed in the time domain. Examining the deviation of the reconstructed signal from the known initial input signal allows instantaneous identification of damage without requiring a baseline signal representing the undamaged state for comparison. The concept of TRA has been extended to guided wave propagations within the CFRP-strengthened reinforced concrete (RC) beams to improve the detectibility of local debonding. Monotonic and fatigue load tests of large-scale CFRP-strengthened RC beams are conducted to demonstrate the potential of the proposed reference-free debonding monitoring system. Comparisons with an electro-mechanical impedance method and an inferred imaging technique are provided as well.