The history of Mesas began with the arrival of the Hohokam culture about 300 n. c. These residents are the source of the original irrigation channels, which were among the most developed in the New World. Some of them traveled more than 20 kilometers across the desert. By the year 1100 an area of 45,000 hectares could be irrigated. By 1450, the network of channels had grown over several hundred kilometers, and many of these lines are still in use today.

Little is known about the period between the disappearance of Hohokam culture and the emergence of the first European settlers, and the first explorers on the American continent did not come to this area. At the end of the 19th century, the U.S. Army subdued the Apache, and the land became settled.

Daniel Webster Jones led an expedition to establish a moral settlement in Arizona. He left St. George, Utah in March 1877, and with others he went to Lehi, just north of today's Mesa, where he founded a settlement known as Jonesville and Fort Utah, which only became Lehi in 1883.

At the same time, a group of settlers arrived from Utah and Idaho. The leaders of these people were named Crismon, Pomeroy, Robson, and Sirine, but they did not want to settle in the settlement founded by Jones, but settled above the Table Mountain, which gave the settlement its name. They dug irrigation ditches, exploiting the original Hohokam-culture structures and started irrigation in April 1878. A second group of settlers arrived in 1879 and settled further east. They called their settlement Stringtown.

On July 17, 1878, Mesa City was registered as a city with an area of one square mile. In 1879 the first school was founded. When Mesa City had about 300 inhabitants in 1883, Mesa City was newly founded as a city. Dr. A. J. Chandler, who later founded Chandler, worked in 1895 to broaden the Mesa Canal in 1895 to allow enough water to flow through to build a power station. This power plant was purchased by the Municipality in 1917. The revenues from this were used to cover the local budget until the 1960s. During the Great Depression, workers paid for by the Works Progress Administration teamed the streets, built a hospital, a town hall, and a library.

When Falcon Field and Williams Field were established in the early 1940s, a large number of military personnel entered the area. Population growth has increased, contributing to the proliferation of air-conditioning systems and the emergence of tourism. In the 1950's and 1960's, industry, especially aircraft production, continued to grow. In the late 1960s, about half of the population was employed in agriculture, but this share has since decreased due to the urbanization of the Phoenix region.

National Register of Historic Places

A number of buildings and objects in Mesa have been added to the National Register of Historic Places:

Museums in Mesa

• Arizona Museum for Youth
• Commemorative Air Force Museum
• Mesa Historical Society and Museum
• Mesa Southwest Museum
• Sirine House

• Caraz, Peru

• Chuck Puleo (* 1972), dartplayer
• Noah Antwiler (* 1980), Comedian
• April Steiner Bennett (* 1980), Chief of Staff and Olympic athlete
• Brea Bennett (* 1987), porn actress
• Christina Birch (* 1986), American cyclist
• Art Bisch (1926-1958), car racer
• Danielle Fishel (* 1981), actress
• Lyndsey Fry (* 1992), ice hockey and inline hockey player
• John Hatch (* 1996), volleyball player
• Todd Heap (* 1980), American football player
• Misty Hyman (* 1979), Olympic athlete
• Harper Kamp (* 1988), basketball player
• Alex Meraz (* 1985), actor
• Paul Perkins (* 1994), American football player
• John Jacob Rhodes III (1943-2011), politician, member of the House of Representatives
• Dave Spina (* 1983), ice hockey player
• Delbert L. Stapley (1896-1978), Apostle of the Church of Jesus Christ of Latter-day Saints
• Wayne Thiebaud (born 1920), painter and prominent American pop artist
• Jimmy Eat World, band
• Authority Zero