The Cahuilla people were the original inhabitants of the land where Mecca now sits, using the area as part of their territory in the Colorado Desert. The De Anza expedition passed through in 1774, one of the earliest documented contacts between Cahuilla people and Spanish colonial forces moving through the region. The Southern Pacific Railroad arrived in 1869, establishing the infrastructure that would eventually make commercial agriculture possible. Date palms were introduced to the area in the late 1890s, when growers recognized that the Coachella Valley's extreme heat, reliable sunshine, and alkaline soil could support the same crop that sustained communities in North Africa and the Middle East. The palm groves that line the roads east of Mecca today are the descendants of those early plantings.

In 1966, director Roger Corman brought his camera crew to Mecca to film The Wild Angels — a biker film starring Peter Fonda and Nancy Sinatra that became a landmark of American exploitation cinema. Corman was drawn by the landscape and the economics of filming in a place that offered authentic settings at low cost. The film's opening sequences used the Mecca area's heat-bleached roads and desert margins to establish a tone of social marginality that matched its subject matter. It was a brief, specific kind of fame — the kind that comes from a place being useful rather than celebrated — but it left a documented mark on the town's history.

The Farmworker Service Center that opened in Mecca in 2005 came after federal investigators at the Department of Housing and Urban Development found a pattern of discrimination in how the region's farmworker communities had been treated by service providers. The center was a response to documented failure. In 2011, the largest Boys and Girls Club unit in California opened in Mecca — a scale that reflected the depth of need in a community where children had historically had few institutional resources. These facilities arrived late, after decades of inadequate investment, in a community whose labor had been fundamental to the regional economy throughout that same period.