The invention discloses a multi-material combination concealed-joint relief fresco which is formed by combining multiple pieces of materials, wherein each piece of material is divided into three layers: an engraving layer positioned on the surface layer and used for the engraving creation of an artist, a concealed-joint structure layer on the second layer, and a mortise-tenon structure layer on the innermost layer; a concave-convex matching part is arranged on the tenon-mortise structure layer so that adjacent materials are in mortise-tenon joint through the concave-convex part; and the connection joint can be covered by the concealed-joint structure layer. A preparation method of the relief fresco comprises the following steps: determining the number, material, thickness and dimension of the combination materials according to the design paper; processing an engraving layer, a concealed-joint structure layer and a mortise-tenon structure layer on each piece of material; processing a concave-convex matching part on the mortise-tenon structure layer of the materials in connected relation; performing artistic creation on the engraving layers by the artist; and connecting all materials in mortise-tenon manner to form a whole relief fresco. The relief fresco disclosed by the invention has diverse materials and rich colors; the dimension is not limited by the material size; multiple materials are occluded through the mortise-tenon structure while the joints are concealed inside; and the whole relief fresco is beautiful and elegant.