A unified constitutive model (UCM) coupled with a continuum damage model (CDM) is developed to design and evaluate high-temperature components in the energy, aerospace, and petrochemical industries. While different constitutive models can predict certain aspects of thermomechanical creep-fatigue responses, a generally applicable model for both short and long-term responses, including stress relaxation and tertiary creep/damage, and strain softening has not been available. Hence, this study unifies strain-focused viscoplastic and creep-rupture-focused damage models to predict fatigue, creep, and creep-fatigue interactions using a single set of model parameters. Two CDMs, Kachanov and isotropic damage, are evaluated by coupling these with a modified Chaboche UCM. The strengths and limitations of the original Kachanov and isotropic damage models in predicting a broad set of low-cycle fatigue and creep responses for a commercially important material, modified Grade 91 steel, are determined. Based on the evaluations, a modified isotropic damage model is proposed. The proposed UCM-CDM is experimentally validated against a large set of modified Grade 91 steel responses, including cyclic softening, rate-dependence, short-term stress relaxation, long-term creep, thermomechanical fatigue, and creep-fatigue interaction at temperatures 400 to 625°C. The UCM is further validated by simulating a set of modified Grade 91 steel notch specimen creep responses. The modified UCM is demonstrated to simulate the influence of stress triaxiality and prior fatigue on creep rupture life. Finally, the proposed UCM is evaluated by analyzing a thick cylinder under thermal transient loading to demonstrate the modified UCM’s applicability for the design and evaluation of high-temperature components.