Most signals between chips or packages in an electric circuit board require certain delays in order to achieve good timing. An extension of the circuit line that is proportional to the designated time delay has been a usual practice due to cost effectiveness. However, the layout of the line becomes dense due to the small size of packages or circuit boards, and this generates crosstalk, causing signal detection errors. In this paper, a design methodology of delay line layout for crosstalk minimization is developed using the genetic algorithm (GA). The GA requires a large number of function evaluations, and efficient calculation of crosstalk is proposed together with a new technique of generating random line, making offsprings, and mutation. Different optimum results have been obtained for different objectives and compared. Some of the designs were actually manufactured and experimentally tested, showing the validity of the optimum results.