The area's first settlers for thousands of years were Native American cultures and historic tribes. Their descendants now occupy the Cocopah and Quechan reservations.

In 1540, Spanish colonial expeditions under Hernando de Alarcón and Melchior Díaz visited the area and immediately recognized the natural crossing of the Colorado River as an ideal spot for a city. The Colorado River narrows to slightly under 1,000 feet (300 m) wide in one area. Military expeditions that crossed the Colorado River at the Yuma Crossing include Juan Bautista de Anza (1774), the Mormon Battalion (1848) and the California Column (1862).

During and after the California Gold Rush to the late 1870s, the Yuma Crossing was known for its ferry crossings for the Southern Emigrant Trail. This was considered the gateway to California, as it was one of the few natural spots where travelers could cross the otherwise very wide Colorado River.

Following the United States establishing Fort Yuma, two towns developed one mile downriver. The one on the California side was called Jaeger City, named after the owner of Jaeger's Ferry, which crossed the river there. It was for a time the larger of the two, with the Butterfield Overland Mail office and station, two blacksmiths, a hotel, two stores, and other dwellings.

The other was called Colorado City. Developed on the south side of the river in what is now Arizona by speculator Charles Poston, it was the site of the custom house. When started, it was just north of the border between Mexican-ruled Sonora, Mexico and California. After the Gadsden Purchase by the United States, the town bordered on the Territory of New Mexico. This area was designated as the Territory of Arizona in 1863. The Colorado City site at the time was duly registered in San Diego; both banks of the Colorado River just below its confluence with the Gila were recognized as being within the jurisdiction of California. The county of San Diego collected taxes from there for many years.

From 1853 a smaller settlement, Arizona City, grew up on the high ground across from the fort and was organized under the name of its post office in 1858. It had adobe dwellings, two stores and two saloons. Colorado City and Jaeger City were almost completely destroyed by the Great Flood of 1862 and had to be rebuilt on higher ground. At that time Colorado City became part of Arizona City. It took the name Yuma in 1873.

From 1854, Colorado City was the major steamboat stop for traffic up and down the Colorado River. After the 1862 flood, it became part of Arizona City. The steamboats transported passengers and equipment for the various mines and military outposts along the Colorado; Colorado City was the terminus of wagon traffic up the Gila River into New Mexico Territory. They offloaded the cargo from ships at the mouth of the Colorado River at Robinson's Landing and from 1864 at Port Isabel. From 1864, the Yuma Quartermaster Depot, today a state historic park, supplied all forts in present-day Arizona, as well as large parts of Colorado and New Mexico. After Arizona became a separate territory, Yuma became the county seat for Yuma County in 1871, replacing La Paz, the first seat.

The Southern Pacific Railroad bridged the river in 1877, and acquired George Alonzo Johnson's Colorado Steam Navigation Company, the only steamboat company on the river. Yuma became the new base of navigation on the river, ending the need for Port Isabel, which was abandoned in 1879. The warehouses and shipyard there were moved to Yuma.

Yuma first appeared on the 1860 U.S. Census as the village of "Arizonia" (Arizona City) in what was then Arizona County, New Mexico Territory (see Arizona City (Yuma, Arizona) for details). It returned as Arizona City in 1870 and then became Yuma in 1873. On April 12, 1902, the village of Yuma was incorporated as a town. It formally incorporated as a city on April 7, 1914.

As of the census of 2010, there were 93,064 people. There were 38,626 housing units in Yuma city, 79.5% of which were occupied housing units. The racial makeup of the city was 68.8% White, 3.2% Black or African American, 1.8% Native American, 1.9% Asian, 0.2% Pacific Islander, and 4.5% from two or more races. 54.8% of the population were Hispanic or Latino of any race.

As of the census of 2000, there were 77,515 people, 26,649 households, and 19,613 families residing in the city. The population density was 726.8 people per square mile (280.6/km²). There were 34,475 housing units at an average density of 323.3 per square mile (124.8/km²). The racial makeup of the city was 68.3% White, 3.2% Black or African American, 1.5% Native American, 1.5% Asian, 0.2% Pacific Islander, 21.4% from other races, and 3.9% from two or more races. 45.7% of the population were Hispanic or Latino of any race.

There were 26,649 households, out of which 38.8% had children under the age of 18 living with them, 56.6% were married couples living together, 13.1% had a female householder with no husband present, and 26.4% were non-families. 21.7% of all households were made up of individuals, and 9.8% had someone living alone who was 65 years of age or older. The average household size was 2.79 and the average family size was 3.27.

In the city, the population was spread out, with 29.6% under the age of 18, 11.9% from 18 to 24, 27.1% from 25 to 44, 17.5% from 45 to 64, and 13.9% who were 65 years of age or older. The median age was 31 years. For every 100 females, there were 99.1 males. For every 100 females age 18 and over, there were 97.2 males.

According to the 2006 American Community Survey estimate, the median income for a household in the city was $39,885, and the median income for a family was $41,588. Males had a median income of $35,440 versus $27,035 for females. The per capita income for the city was $18,393. About 14.1% of families and 16.9% of the population were below the poverty line, including 23.4% of those under age 18 and 13.9% of those age 65 or over.

High unemployment remains an issue in Yuma. Citing April 2014 data, the Bureau of Labor Statistics ranked Yuma as having the highest unemployment rate in the United States at 23.8 percent, above the 21.6 percent in El Centro, California. Yuma's agricultural workforce, which adjusts to the picking season, is cited by the Arizona Department of Commerce as the reason for the apparent high unemployment.