An ab initio electronic structure method is developed to describe electron transfer in large systems. The method is based on a molecular fragment effective Hamiltonian approach. The strategy pieces together results of ab initio quantum chemistry calculations on overlapping molecular segments in order to build an effective Hamiltonian that describes the long-range electronic interactions. This is accomplished by constructing fragment effective Hamiltonians that properly describe the electronic propagation characteristics of each fragment (computed at the ab initio Hartree-Fock level in an appropriate basis set). The fragment effective Hamiltonian is projected onto the valence orbital space of each fragment, and a relatively well-localized set of effective interactions is obtained. Combining these projected fragment Hamiltonians allows the construction of a valence effective Hamiltonian for the entire system. We find that the fragment Hamiltonian matrices constructed in this way are transferable between donor-acceptor systems with homologous electron-transfer bridges. The overall strategy of fragmentation and construction of valence effective Hamiltonians could enable ab initio quality computations of long-range tunneling interactions in macromolecules. We demonstrate the use of the method in a series of electron-transfer model systems of modest size.