Cardiovascular disease (CVD) is a leading cause of death worldwide. Clinically, CVD includes a wide range of pathologies that result in structural remodeling and functional adaptations in cardiovascular tissues, leading to heart failure and ultimately death if left untreated. Using an engineering approach, cardiovascular performance in CVD can be evaluated by measuring vascular and ventricular function, which are coupled in healthy states and uncoupled in disease. Limiting assessment only to vascular or ventricular tissues hinders the ability to understand the global cardiovascular consequences of CVD. The work in this dissertation focuses on the characterization of cardiovascular biomechanics in healthy conditions and several disease states. Stiffening of large proximal arteries impairs conduit and damping function, is associated with hypertension and aging, and serves as a prognostic indicator for CVD. Here, arterial stiffness was evaluated using experimental testing measurements and constitutive modeling analyses in small and large animal models. The data show that mitochondria DNA mutations lead to the development of hypertension and age-related arterial stiffening. I also report that stiffening can be differentiated into strain-induced and remodeling-induced modalities in a chronic model of pulmonary hypertension. Increased loading on the ventricle due to hypertension or arterial stiffening leads to ventricular hypertrophy and a reduced coupling efficiency with the vasculature. Here, ventricular function and ventricular-vascular coupling were evaluated using a pressure-volume technique. The data show that limiting collagen turnover via intrinsic resistance to degradation results in beneficial effects for the right ventricle in pulmonary arterial hypertension. I also demonstrate that left and right ventricular function are preserved despite disruption of collagen synthesis. The biomechanical assessment of vascular and ventricular function used here via cardiac catheterization, ex vivo mechanical testing, echocardiography, and histological staining can be used as a framework for future studies independent of species or diseases. Characterizing the individual mechanical adaptations in the heart and arteries in response to a stimulus, e.g. pressure in hypertensive conditions, and relating these changes between vascular and ventricular tissues can lead to i) understanding disease development processes, ii) identifying indices that can have prognostic value for CVD patients, and iii) developing novel disease treatments.