In 1903 an overland trail was cut from Valdez to Fairbanks, and a roadhouse was established a short time later at the junction of the Delta and Tanana Rivers. In 1904 the U.S. Army Signal Corps built the McCarty Telegraph Station. Rika's Roadhouse was built in 1910. Ongoing mining activity just north of Delta Junction in the Tenderfoot area, and the Chisana Gold Strike of 1913, brought many prospectors and other travelers through the area. It became known as Buffalo Center in 1927, for the American bison that were transplanted here in the 1920s. In 1942, construction of the Alaska Highway began, and a military base (later Ft. Greely) was completed 5 miles to the south. In 1946, a dairy farm was established; beef cattle were brought in during 1953 by homesteaders. Construction of the Trans-Alaska Pipeline between 1974 and 1977 brought a dramatic upswing to the population and economy. In 1978, the State began Delta Agricultural Project I, creating 22 farms averaging 2,700 acres each. In 1982, the Delta II project formed 15 additional farms, averaging more than 1,600 acres each. Tracts of 2,000 to 3,600 acres were sold by lottery, and State loans were made available to purchase and clear the land. The 70,000-acre Delta Bison Range was created in 1980 to confine the bison and keep them out of the barley fields. Deltana's location at the junction of two major highways has also brought development based on services to travelers.
3.8% of the population are Alaska Native or part Native. Deltana is a relatively large area, with over 650 homes. Residents are primarily non-Native.

During the 2000 U.S. Census, there were 669 total housing units, and 130 were vacant. 98 of these vacant housing units are used only seasonally. 583 residents were employed. The unemployment rate at that time was 12.75%, although 48.54% of all adults were not in the work force. The median household income was $50,066, per capita income was $18,446, and 15.08% of residents were living below the poverty level.

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