In the years immediately preceding the period of the Republic of Texas, settlers and traders began migrating to the rolling prairie now included in Grayson County. With a slow but steady increase in population, in the early days of statehood the legislature created (1846) the county out of territory theretofore included in Fannin County.

In the history of the county, certain geological and geographical features have played a most significant role. Most conspicuous is Red River which, together with Lake Texoma since the 1940s, forms the northern boundary. On the western side, the region of the Cross Timbers has been quite influential, particularly in the early days. Blackland prairie is a dominant feature for much of the county, while in the western section sandy soil identified with the Woodbine formation is very pronounced. The Preston Anticline is an unusually interesting geological feature which has greatly influenced the availability of mineral resources.

Prior to the coming of the railroads in the 1870s, the local economy centered upon agriculture. The rolling blackland prairie contributed to the emergence of cotton as a dominant product, while elsewhere diversified agricultural and livestock pursuits were observed. Subsequent to the introduction of the iron horse, industrial activity commenced to expand, a trend which accelerated during the twentieth century.

Early in the life of the county, settlers evidenced concern for churches, schools, and cultural activities. Before the inception of the public school system, private schools abounded. At one time, because of the number of institutions of higher learning, the county seat was known as the Athens of Texas. Throughout the county many churches were established, many of which have long since held their centennial celebration. In the latter 19th century, perhaps the finest opera house southwest of St. Louis was located in Sherman.

Not to be forgotten is the fact that throughout the 19th century, the Indian Territory lay just across Red River from the county. From "Trail of Tears" days and after Oklahoma statehood, the land and people across the river had a prominent impact upon the history of the county.

The county has produced its share of men and women who have risen to national prominence, most notable of whom was General Dwight D. Eisenhower. Similarly, it has experienced its proportion of unusual events, but these events have been recorded elsewhere.