Quantitative measurements of inherently three-dimensional (3D) cardiac strain and strain rate require 3D data; MRI provides uniquely high sensitivity to material strain by combining phase contrast with single-shot acquisition methods, such as echo-planar imaging (EPI). Previous MRI methods applied to 3D strain used multiple two-dimensional (2D) acquisitions and suffered loss of sensitivity due to magnification within the strain calculation of physiologic noise related to cardiac beat-to-beat variability. In the present work, each single-shot acquisition generates 3D image data by acquiring two contiguous 2D Fourier transform (FT) images in a single echo train of an EPI readout. Although strain encoding divides across multiple EPI shots, each strain component is computed only within single-shot data, avoiding noise magnification. Strain tensor maps are displayed using iconic 3D graphics or a simple color code of tensor shape. In a deforming gel phantom, gradient-recalled echo (GRE) MRI movies of 3D strain rates match expected strain fields. In normal human subjects, 3D strain rate tensor movies of heart and brain comprising seven slices in each of seven cardiac phases were completed in 56 heartbeats. Stimulated echo (STE) MRI of net systolic 3D strain was also demonstrated. Two-slices-in-one-shot spatial encoding permits a complete quantitative survey of ventricular 3D strain in under a minute, with routine patient supervision and turnkey image processing.