Although biomimetic designs are expected to play a key role in exploring future structural materials, facile fabrication of bulk biomimetic materials under ambient conditions remains a major challenge. Here, we describe a mesoscale "assembly-and-mineralization" approach inspired by the natural process in mollusks to fabricate bulk synthetic nacre that highly resembles both the chemical composition and the hierarchical structure of natural nacre. The millimeter-thick synthetic nacre consists of alternating organic layers and aragonite platelet layers (91 weight percent) and exhibits good ultimate strength and fracture toughness. This predesigned matrix-directed mineralization method represents a rational strategy for the preparation of robust composite materials with hierarchically ordered structures, where various constituents are adaptable, including brittle and heat-labile materials.