The atomic point-charge model used in most molecular mechanics force fields does not represent well the electronic anisotropy that is featured in many directional noncovalent interactions. Sulfur participates in several types of such interactions with its lone pairs and σ-holes. The current study develops a new model, via the addition of off-atom charged sites, for a variety of sulfur compounds in the OPLS-AA and OPLS/CM5 force fields to address the lack of charge anisotropy. Parameter optimization is carried out to reproduce liquid-state properties, torsional and noncovalent energetics from reliable quantum mechanical calculations, and electrostatic potentials. Significant improvements are obtained for computed free energies of hydration, reducing the mean unsigned errors from ca. 1.4 to 0.4-0.7 kcal/mol. Enhanced accuracy in directionality and energetics is also obtained for molecular complexes with sulfur-containing hydrogen and halogen bonds. Moreover, the new model reproduces the unusual conformational preferences of sulfur-containing compounds with 1,4-intramolecular chalcogen bonds. Transferability of the new force field parameters to cysteine and methionine is verified via molecular dynamic simulations of blocked dipeptides. The study demonstrates the effectiveness of using off-atom charge sites to address electronic anisotropy, and provides a parametrization methodology that can be applied to other systems.