Alterations in trans‐sarcolemmal and sarcoplasmic reticulum (SR) Ca²⁺ fluxes may contribute to impaired cardiomyocyte contraction and relaxation in heart failure. We investigated the mechanisms underlying heart failure progression in mice with conditional, cardiomyocyte‐specific excision of the SR Ca²⁺‐ATPase (SERCA) gene. At 4 weeks following gene deletion (4‐week KO) cardiac function remained near normal values. However, end‐stage heart failure developed by 7 weeks (7‐week KO) as systolic and diastolic performance declined. Contractions in isolated myocytes were reduced between 4‐ and 7‐week KO, and relaxation was slowed. Ca²⁺ transients were similarly altered. Reduction in Ca²⁺ transient magnitude resulted from complete loss of SR Ca²⁺ release between 4‐ and 7‐week KO, due to loss of a small remaining pool of SERCA2. Declining SR Ca²⁺ release was partly offset by increased L‐type Ca²⁺ current, which was facilitated by AP prolongation in 7‐week KO. Ca²⁺ entry via reverse‐mode Na⁺–Ca²⁺ exchange (NCX) was also enhanced. Up‐regulation of NCX and plasma membrane Ca²⁺‐ATPase increased Ca²⁺ extrusion rates in 4‐week KO. Diastolic dysfunction in 7‐week KO resulted from further SERCA2 loss, but also impaired NCX‐mediated Ca²⁺ extrusion following Na⁺ accumulation. Reduced Na⁺‐K⁺‐ATPase activity contributed to the Na⁺ gain. Normalizing [Na⁺] by dialysis increased the Ca²⁺ decline rate in 7‐week KO beyond 4‐week values. Thus, while SERCA2 loss promotes both systolic and diastolic dysfunction, Na⁺ accumulation additionally impairs relaxation in this model. Our observations indicate that if cytosolic Na⁺ gain is prevented, up‐regulated Ca²⁺ extrusion mechanisms can maintain near‐normal diastolic function in the absence of SERCA2.