GAMESS (US) can perform several general computational chemistry calculations, including Hartree–Fock method, density functional theory (DFT), generalized valence bond (GVB), and multi-configurational self-consistent field (MCSCF). Correlation corrections after these SCF calculations can be estimated by configuration interaction (CI), second order Møller–Plesset perturbation theory (MP2), and coupled cluster (CC) theory. Solvent effect can be considered using quantum mechanics and molecular mechanics through discrete effective fragment potentials or continuum models (such as PCM). Relativistic corrections can be calculated, including third order Douglas-Kroll scalar terms.
While the program does not directly perform molecular mechanics, it can do mixed quantum mechanics and molecular mechanics calculations through effective fragment potentials or through an interface with the Tinker code. The fragment molecular orbital method can be used to treat large systems, by dividing them into fragments.
It can also be interfaced with the valence bond VB2000 and XMVB programs and the Natural Bond Orbital (NBO) population analysis program.
The input files use a keyword based scheme. For example, $CONTRL SCFTYP=ROHF MAXIT=30 $END, which specifies that the SCF part of the code should do an restricted open-shell Hartree–Fock (ROHF) calculation and quit if the result does not converge in 30 iterations. The output is in an English language text file.