We present a simple yet elegant Mueller matrix approach for controlling the Fano interference effect and engineering the resulting asymmetric spectral line shape in anisotropic optical system. The approach is founded on a generalized model of anisotropic Fano resonance, which relates the spectral asymmetry to two physically meaningful and experimentally accessible parameters of interference, namely, the Fano phase shift and the relative amplitudes of the interfering modes. The differences in these parameters between orthogonal linear polarizations in an anisotropic system are exploited to desirably tune the Fano spectral asymmetry using pre- and post-selection of optimized polarization states. Experimental control on the Fano phase and the relative amplitude parameters and resulting tuning of spectral asymmetry is demonstrated in waveguided plasmonic crystals using Mueller matrix-based polarization analysis. The approach enabled tailoring of several exotic regimes of Fano resonance including the complete reversal of the spectral asymmetry. The demonstrated control and the ensuing large tunability of Fano resonance in anisotropic systems shows potential for Fano resonance-based applications involving control and manipulation of electromagnetic waves at the nano scale.