The capability to perform depletion analysis of pebble bed reactors has been traditionally limited to a few dedicated codes that are designed for helium-cooled reactors, rely on pregenerated problem-dependent group cross sections, and have limited flexibility in the materials and in the geometries they can model. This paper presents a newly developed tool to search for pebble bed reactor core equilibrium composition and calculate its neutronic characteristics. It uses MCNP for transport calculations and ORIGEN2 for depletion calculations and can generate effective one-group cross sections “on-the-fly” as pebbles move through the core using point-energy cross sections. This tool can be used for any coolant type including liquid salt, can model complex geometries, and can account for any level of heterogeneity. Also developed are two simplified methodologies that are based on unit-cell analysis and can considerably reduce the required computational time; they are useful for parametric studies.