The area around modern Lefors was near the heart of Comancheria and a common village site for the nomadic tribes of Comanche.

The Battle of the North Fork of the Red River, between the U.S. Army under the command of Ranald Slidell Mackenzie and the Comanche, was fought near here on September 29, 1872.

The town was named for Perry LeFors, who traveled with his father to the Panhandle in 1878 and later became foreman of the Diamond F Ranch, a part of the Francklyn Land and Cattle Company, which became insolvent in 1886 and became the White Deer Lands Trust Company, of which Timothy Dwight Hobart was the agent.

[4] In 1882, the first homestead on the future townsite was laid by Travis Leach, a rancher and surveyor, whose log cabin served as a stagecoach stop on the mail route from Fort Elliott and Mobeetie to Tascosa.

The population reached 150 in 1910, and despite its small size and the lack of a railroad, the town managed for a time to remain the county seat.

By 1931, Lefors had incorporated, and in 1932, the town finally obtained a railroad, when the Fort Worth and Denver extended its line from Pampa.

[5][6][7][8] The town suffered a flood in 1961, unemployment from the closure of several area carbon black plants in 1964, and a tornado in 1975.

According to the United States Census Bureau, the town has a total area of 0.4 square miles (1.0 km2), all land.

Lefors is on the North Fork of the Red River and State Highway 273, 12 miles southeast of Pampa in central Gray County.

Lefors ISD offers football, tennis, golf, basketball, cross country, and track and field through its athletic department, as well as academic UIL.