In this paper, the compression behavior of sand-marine clay mixtures was investigated, both experimentally and theoretically. The test data reveal that the Normal Compression Line of a sand-clay mixture depends on both the sand fraction and the initial water content of the clay matrix. The local stress in the clay matrix σ′c is approximately close to the overall stress of the sand-clay mixture σ′ for a sand mass fraction of 20%. The stress ratio, σ′c/σ′, falls significantly with increasing overall stress for a sand fraction of 60%, which may be attributed to the formation of clay bridges between adjacent sand particles. A compression model was formulated within the homogenization framework. First, a homogenization equation was proposed, which gives a relationship between the overall stiffness E and that of the clay matrix Ec. Then, a model parameter ξ was incorporated considering the sensitivity of the structure parameter on the volume fraction of the clay matrix. Finally, a simple compression model with three model parameters was formulated using the tangent stiffness. Comparisons between the experimental data and simulations reveal that the proposed model can well represent the compression curves of the sand-marine clay mixtures observed in the laboratory.