Simulation involves predicting responses of a physical system. In this article, we simulate opto-acoustic signals generated in a three-dimensional volume due to absorption of an optical pulse. A separable computational model is developed that permits an order-of-magnitude improvement in computational efficiency over a non-separable model. The simulated signals represent acoustic waves, measured by a probe with a linear transducer array, in a rotated and translated coordinate frame. Light is delivered by an optical source that moves with the probe's frame. A spatio-temporal impulse response for rectangularelement transducer geometry is derived using a Green's function solution to the acoustic wave equation. The approach permits fast and accurate simulation for a probe with arbitrary trajectory. For a 3D volume of n 3 voxels, computation is accelerated by a factor of n. This may potentially have application for opto-acoustic imaging, where clinicians visualize structural and functional features of biological tissue for assessment of cancer and other diseases.