The uneven distribution of travel demand is incredibly commonplace in cities, but insufficient attention has been paid to this problem. In this paper, we explore the impact of the uneven distribution of travel demand on an accessible network. A model with a sparse and dense mixed grid transit network based on an uneven distribution of travel demand is proposed to provide a high-performance bus service. The transit network was composed of two parts: a dense grid network in the downtown area and a sparse grid network in the periphery. The objective function of the model included agency cost and passenger cost, where the decision variables were the downtown-to-city ratio, the downtown headway, stop spacing (line spacing), and ratio of the periphery headway to the downtown headway. This study validated the proposed model using the demands of San Francisco. The concentrated spatial demand resulted in a lower total cost, whereas the varying travel demand must be controlled within an appropriate range to maintain the bus performance. The stable bus lines and stops with a variable timetable of the proposed model are profitable for fast-growing cities.