"Sahuarita" roughly translates to "little saguaro." Saguaro cactus have a relatively long lifespan, often exceeding 150 years. Harming or vandalizing saguaros in any manner, such as shooting them (sometimes known as "cactus plugging") is illegal by state law in Arizona and punishable by up to 25 years in jail.

The first known human inhabitants of the Sahuarita region were the Hohokam people, which may be the ancestors of the modern day Tohono O'odham nation. The Hohokam were known for their extensive and highly innovative use of irrigation. They disappeared around 1450 or 1500 under mysterious circumstances, most likely because of a prolonged drought.

Mission San Xavier del Bac was established in 1692 by Father Eusebio Francisco Kino, who founded a chain of Spanish missions in the Sonoran Desert. Unlike the other Spanish missions in Arizona, San Xavier is still actively run by Franciscans, and continues to serve the native community by which it was built. Widely considered to be one of the finest examples of Spanish Colonial architecture in the United States, the Mission hosts some 200,000 visitors each year.

In 1854, following the Gadsden Purchase, the area became a part of the U.S. Territory of New Mexico. It was then part of the Confederate Arizona Territory between 1861 and 1862 before being captured by the Union and incorporated into Arizona Territory in 1863.

The earliest known reference can be found on a German map from 1875, which labels the town "Sahuarito" (with an "o"). The first known U.S. map to list the town came in 1879, by the U.S. Department of Interior, calling the town "Saurita".

In 1915, worried about the possibility of a German blockade of rubber imports, a group of investors including Bernard Baruch, Joseph Kennedy, and J.P. Morgan founded the Continental Farm of Sahuarita along the Santa Cruz River with hopes of growing guayule (Parthenium argentatum), a plant that can be used to make rubber. The project was abandoned after the end of World War I, and in 1922, was sold to Queen Wilhelmina of the Netherlands, who rented the land to cotton farmers.

In 1948, R. Keith Walden relocated the Farmers Investment Co. (FICO) from California to Arizona, buying the Continental Farm lands from Queen Wilhelmina. In 1965, fearing a collapse of the cotton industry because of the advent of new synthetic fibers, Walden switched his crop to pecans. Today, the FICO pecan orchard is the largest in the world, with over 6,000 acres (24 km²) and 106,000 trees.

Camp Continental, a labor camp for German prisoners of war, was one of two major POW camps in the state, along with Camp Papago Park in Phoenix. Established in November, 1944, it was located around what is now Continental Ranch, West of the Nogales Highway and the Quail Crossing Boulevard intersection. The population of 250 POWs provided badly needed labor, mainly tending to cotton and vegetable crops, while most of the country's work force was involved with the war. More than one escape attempt was made by the Germans, but none of them were successful.

25% of land in Sahuarita is designated flood plain.

Sahuarita wasn't incorporated until 1994, when it elected Anna M. Matyas as its first mayor.