We consider the lattice formulation of SO(10) chiral gauge theory with left-handed Weyl fermions in the sixteen dimensional spinor representation (16) within the framework of the Overlap fermion/the Ginsparg-Wilson relation. We propose a manifestly gauge invariant path-integral measure for the left-handed Weyl field using the whole components of the Dirac field, but the right-handed part of which is just saturated completely by inserting a suitable product of the SO(10)-invariant ‘t Hooft vertices in terms of the right-handed field. The definition of the measure applies to all possible topological sectors. The measure possesses all required transformation properties under lattice symmetries and the induced effective action is CP invariant. The global U(1) symmetry of the left-handed field is anomalous due to the non-trivial transformation of the measure, while that of the right-handed field is explicitly broken by the ‘t Hooft vertices. There remains the issue of locality in the gauge-field dependence of the Weyl fermion measure, but the question is well-defined and can be addressed in the weak gauge-coupling expansion at least using Monte Carlo methods without encountering the sign problem.