The graphene-based Field Effect Transistors (GFETs), due to their multi-parameter characteristics, are growing rapidly as an important detection component for the apt detection of disease biomarkers, such as DNA, in clinical diagnostics and biomedical research laboratories. In this paper, the non-equilibrium Green function (NEGF) is used to create a compact model of GFET in the ballistic regime as an important building block for DNA detection sensors. In the proposed method, the self-consistent solutions of two-dimensional Poisson’s equation and NEGF, using the nearest neighbor tight-binding approach on honeycomb lattice structure of graphene, are modeled as an efficient numerical method. Then, the eight parameters of the phenomenological ambipolar virtual source (AVS) circuit model are calibrated by a least-square curve-fitting routine optimization algorithm with NEGF transfer function data. At last, some parameters of AVS that are affected by induced charge and potential of DNA biomolecules are optimized by an experimental dataset. The new compact model response, with an acceptable computational complexity, shows a good agreement with experimental data in reaction with DNA and can effectively be used in the plan and investigation of GFET biosensors.