This paper contributes a new matrix method for the solution of high-order linear complex differential equations with variable coefficients in rectangular domains under the considered initial conditions. On the basis of the presented approach, the matrix forms of the Bernoulli polynomials and their derivatives are constructed, and then by substituting the collocation points into the matrix forms, the fundamental matrix equation is formed. This matrix equation corresponds to a system of linear algebraic equations. By solving this system, the unknown Bernoulli coefficients are determined and thus the approximate solutions are obtained. Also, an error analysis based on the use of the Bernoulli polynomials is provided under several mild conditions. To illustrate the efficiency of our method, some numerical examples are given.