Denton County was officially established by the Texas Legislature on April 11, 1846. Anglo settlement began just a few years earlier after William S. Peters of Louisville, Kentucky and a group of twenty investors obtained a land grant from the Texas Congress in 1841. The land settled by their company, the Texian Land and Immigration Company, became known as the Peters colony. Their grant included all of the future Denton County, as well as parts or all of several other future counties. The earliest settlement in what became Denton County was in the southeastern section, near the site of present Hebron, and most of the early residents took up land in the Cross Timbers area.

Denton County was established out of what had been a much larger Fannin County. The county was named for John Bunyan Denton, an eastern Fannin County Methodist preacher and lawyer, who was killed in a raid against Indians in northern Tarrant County on May 22, 1841. The county seat, named Pinckneyville in honor of the first governor of Texas, was established very near the present center of the City of Denton. Although county officials were elected in 1846, no courthouse was built, and less than two years later a site named Alton, three or four miles to the southeast, was made county seat. Water shortages caused the move, and Alton moved yet again in 1850 to Hickory Creek. A log courthouse, the first in the county, was built there. Alton soon had stores, residences, a hotel, and was a regular stage stop. In the summer of 1856, however, county residents voted to establish a new county seat near the center of the county on a donated 100-acre tract. The new town, named Denton, was established the next year but was not incorporated as a city until 1866.

Construction of the present Courthouse-on-the-Square began in 1895. The cornerstone was laid in 1896, and the courthouse was dedicated in 1897. The Courthouse was then restored in 1987 to its present condition.

Transportation was vital to the growth of the Denton area. Railroads entered the county in the 1880s and had a great economic and demographic effect. Nearly a century later, the county saw its greatest growth with the arrival of Interstate 35 East, built in the 1950s and later joined by Interstate 35 West in the 1970s. Dallas-Fort Worth International Airport opened in January 1974. Denton County has been one of the most rapidly growing counties in the United States for decades.

Denton is the proud home of two public universities, Texas Woman's University and the University of North Texas, which is the third largest university in the State of Texas. The two universities have a combined enrollment of approximately 40,000 students. The University of North Texas, originally named the North Texas Normal College, was established in 1890, while legislation authorizing the establishment of the Girls College of Industrial Arts, now Texas Woman's University, was passed in 1901.

Denton is also home to a thriving music scene, thanks in part to the area’s universities. The Grammy Award winning bands Brave Combo and One O’Clock Lab Band are both from Denton, as are UNT alumni Don Henley, Roy Orbison and Pat Boone.