The town of Mantua was established about 3 miles southwest of here in 1854. Mantua prospered but was unexpectedly bypassed in 1873 when the Houston and Texas Central Railway (H&TC) extended its track through this area instead. That year a depot was built and a post office established in the new town named for Maria Van Alstyne, the widow of W. A. Van Alstyne who had been a principal stockholder of the H&TC.
Churches, businesses, and people of Mantua and other area towns moved here to be near the railroad. Van Alstyne was incorporated and a newspaper established in 1883. Columbia College was founded in 1889.
Van Alstyne contained banks, schools, hotels, an opera house, a literary club, and electric service by 1900, when cotton and other farm production dominated the local economy. Interurban transportation began in 1908. The local "Grays" semi-pro baseball team, established about 1902, played for many decades and produced a number of major league players.
Many local businesses, churches, and social organizations trace their origins to Mantua and 19th century Van Alstyne. The historic downtown area, the former site of popular Saturday night social activities, continues as a business and social center.