[3] Long settled by Native Americans of indigenous cultures for thousands of years, this area was controlled by the Spanish Empire in the colonial era.

[4] The county territory was defined as being west of longitude 113° 20' and south of the Bill Williams River.

[5] Its original boundaries remained the same until 1982, when La Paz County was created from its northern half.

[8]: 326 During the winter agricultural season from November to March, some 40,000 Mexican workers cross the border daily to work in United States fields.

[10] The area is watered by the Colorado River, and the sector supplies a large part of the US leafy vegetables.

In 2017 the county produced vegetables worth $782,293,000, ranking first in the state and third in the entire country, from 107,908 acres (43,669 ha).

[16] In this county, plantations suffer from the Carob Moth (Ectomyelois ceratoniae) and the Banks Grass Mite (Oligonychus pratensis).

[16] Leaders in the county are aware their economy is tied to that of Mexican states on the other side of the border; both have to be considered.

On the American side, there is a mix of retail stores, warehouses and trucking companies..."[10] Because of Yuma County's location along the U.S.-Mexico border, large numbers of aliens entering the United States illegally pass through Yuma County.

From October 2004 to July 2005, some 124,400 undocumented foreign nationals were apprehended in the area, a 46% increase over the previous year.

The report from the Congressional Research Service stated, "...it is unclear how much of the drop-off is due to increased enforcement and how much is a result of the U.S. economic downturn and other systemic factors".

[18] [10] The Greater Yuma Economic Development Corp anticipates many agricultural jobs in the county will soon transition to robotics.

[20] The Board adopts ordinances, establishes programs, levies taxes, appropriates funds, appoints certain officials, and zones property and regulates development in the unincorporated area.

[22] However, their margins of victory have been reduced in recent years as the county has rapidly grown in population and become majority-Hispanic.

Donald Trump only won the county by 560 votes over Hillary Clinton in the presidential election of 2016.

In 2024, Trump won Yuma County by over 20 percentage points against Kamala Harris, the best performance by a Republican since Ronald Reagan in 1984.

Southwest of Yuma County, is the entirety of Northwest Mexico, at the north shoreline of the Gulf of California, and the outlet of the Colorado River into the Colorado River Delta region, now altered with lack of freshwater inputs.