Safford was founded by Joshua Eaton Bailey, Hiram Kennedy, and Edward Tuttle, who came from Gila Bend, in southwestern Arizona.

They left Gila Bend in the winter of 1873-74 because their work on canals and dams had been destroyed by high water the previous summer.

It is much hotter than most places in eastern Arizona due to its relatively low elevation of 2,953 feet (900 m) at the Agricultural Center where records are kept, and often reaches temperatures almost as hot as found in Phoenix.

[11] Monastery of St. Paisius, Safford is an Orthodox women's cenobitic community which follows the traditional rule of monastic life.

The monastery, under the jurisdiction of the Russian Orthodox Church Outside of Russia (ROCOR)- Western Diocese is situated in the high Sonoran Desert at the base of Mount Graham.

The city's largest employers are Freeport-McMoRan Copper and Gold, Safford Unified Schools, DRG Technologies Inc, Bowman Consulting Group, Open Loop Energy and Walmart.

The community is served by a freight rail line, the Arizona Eastern Railway, and hosts an air facility, Safford Regional Airport.

ADOT is considering putting a U.S. Route 70 loop south of the city that would run from Swift Trail Junction to Thatcher.

On January 6, 2025, Grand Canyon Scenic Airlines began twice daily flights between Safford and Phoenix Sky Harbor airport.

Safford is also home to the Eastern Arizona College's Discovery Park Campus, a unique public educational destination facility that provides tours of the world-class telescopes at the Mt.

Graham International Observatory, a public access observatory with a research grade 20" Cassagrain telescope, the World's largest permanent mount "Camera Obscura", a full motion Shuttle simulator that takes you on an exciting ride through the Milky Way galaxy, and galleries of historical artifacts from Graham County and the "History of Astronomy" Gallery, as well as a beautifully restored Sonoran riparian area featuring a one-acre ecology education pond and over four miles of trials that take you through the habitat of native and migratory birds, reptiles, and mammals.

[15] Due to Safford's relatively isolated dark sky location, the area has been chosen as a prime spot for hosting observatories.

Safford and Thatcher's street lights are low-output to improve the quality of the images taken by the observatories atop the mountain to the southwest of the city.