AbstractLarge-scale two-dimensional (2D) moiré superlattices are driving a revolution in designer quantum materials. The electronic interactions in these superlattices, strongly dependent on the periodicity and symmetry of the moiré pattern, critically determine the emergent properties and phase diagrams. To date, the relative twist angle between two layers has been the primary tuning parameter for a given choice of constituent crystals. Here, we establish strain as a powerful mechanism to in situ modify the moiré periodicity and symmetry. We develop an analytically exact mathematical description for the moiré lattice under arbitrary in-plane heterostrain acting on any bilayer structure. We demonstrate the ability to fine-tune the moiré lattice near critical points, such as the magic angle in bilayer graphene, or fully reconfigure the moiré lattice symmetry beyond that imposed by the unstrained constituent crystals. Due to this unprecedented simultaneous control over the strength of electronic interactions and lattice symmetry, 2D heterostrain provides a powerful platform to engineer, tune, and probe strongly correlated moiré materials.