Functional imaging of mouse models of cardiac health and disease provides a major contribution to our fundamental understanding of the mammalian heart. However, imaging murine hearts presents significant challenges due to their small size and rapid heart rate. Here we demonstrate the feasibility of high-frame-rate, noninvasive optoacoustic imaging of the murine heart. The temporal resolution of 50 three-dimensional frames per second provides functional information at important phases of the cardiac cycle without the use of gating or other motion-reduction methods. Differentiation of the blood oxygenation state in the heart chambers was enabled by exploiting the wavelength dependence of optoacoustic signals. Real-time volumetric tracking of blood perfusion in the cardiac chambers was also evaluated using indocyanine green. Taken together, the newly-discovered capacities offer a unique tool set for in-vivo structural and functional imaging of the whole heart with high spatio-temporal resolution in all three dimensions.