A detailed experimental investigation was performed at a single maximum cyclic stress (σmax) level to physically characterize the progression of thermomechanical fatigue (TMF) damage in continuously reinforced [0°] SCS-6/TIMETAL 21S, a titanium matrix composite. In-phase (IP) and out-of-phase (OP) loadings were investigated at σmax = 1000 MPa with a temperature cycle from 150 to 650°C. Damage progression, in terms of macroscopic property degradation, was experimentally quantified through an advanced TMF test methodology that incorporates explicit measurements of the isothermal static moduli at the TMF temperature extremes and the coefficient of thermal expansion (CTE) as functions of the TMF cycles. Detailed characterization of the physical damage progression at the micro-structural level was performed by interrupting multiple TMF tests at various stages of mechanical property degradation and analyzing the microstructure through extensive destructive metallography. Further, the extent of damage was also quantified through residual static strength measurements. Results indicated that damage initiation occurred very early in cyclic life (N < 0.1 Nf) for both the IP and OP TMF loadings. IP TMF damage was found to be dominated by fiber breakage with a physical damage progression in the microstructure that was difficult to quantify. OP TMF loadings produced matrix cracking exclusively associated with surface initiations. Here, damage progression was easily distinguished in terms of both the number of cracks and their relative inward progressions toward the outer fiber rows with increased cycling. The point at which the leading cracks reached the outer fiber rows (when localized fiber/matrix debonding and matrix crack bridging occurred) appeared to be reflected in the macroscopic property degradation curves.