In this paper, Hirota’s bilinear method is extended to construct multisoliton solutions of a (2+1)-dimensional variable-coefficient Toda lattice equation. As a result, new and more general one-soliton, two-soliton, and three-soliton solutions are obtained, from which the uniform formula of the N-soliton solution is derived. It is shown that Hirota’s bilinear method can be used for constructing multisoliton solutions of some other nonlinear differential-difference equations with variable coefficients.