A novel methodology is introduced here to generate coarse-grained (CG) representations of molecular models for simulations. The proposed strategy relies on basic graph-theoretic principles and is referred to as graph-based coarse-graining (GBCG). It treats a given system as a molecular graph and derives a corresponding CG representation by using edge contractions to combine nodes in the graph, which correspond to atoms in the molecule, into CG sites. A key element of this methodology is that the nodes are combined according to well-defined protocols that rank-order nodes based on the underlying chemical connectivity. By iteratively performing these operations, successively coarser representations of the original atomic system can be produced to yield a systematic set of CG mappings with hierarchical resolution in an automated fashion. These capabilities are demonstrated in the context of several test systems, including toluene, pentadecane, a polysaccharide dimer, and a rhodopsin protein. In these examples, GBCG yields multiple, intuitive structures that naturally preserve the chemical topology of the system. Importantly, these representations are rendered from algorithmic implementation rather than an arbitrary ansatz, which, until now, has been the conventional approach for defining CG mapping schemes. Overall, the results presented here indicate that GBCG is efficient, robust, and unambiguous in its application, making it a valuable tool for future CG modeling.