Seneca became a division point on the railroad, with a depot, rail yard, and roundhouse, employing over 70 people. Railroad operations brought a measure of prosperity to the town, and promoted its growth. Between 1918 and 1923, the Potash Highway, running from Grand Island to Alliance, was constructed parallel to the Burlington's route; it ran through the center of Seneca. The town boasted a number of retail businesses, including hotels, banks, a lumberyard, a railroad cafe, and an automobile dealership. For some years, it was the largest municipality in Thomas County, reaching a peak population of 476 in 1920.