Carrizo Creek was a landmark long before stagecoach routes formalized it as a station stop. The creek ran at the surface most of the year in a landscape where surface water was a rare enough commodity to organize travel around. Native Americans had used it as a watering place for generations before Spanish explorers, Mexican traders, American fur trappers, and soldiers followed the same logic to the same location. The 1855 Railroad Survey expedition camped at Carrizo in June, describing the geography that made it important: it was simply the place where water existed when water was what travelers needed most.

The military constructed an adobe building at Carrizo in June 1855, which the San Antonio-San Diego Mail Line subsequently adopted as its station. A 1857 correspondent described it as an old adobe house with the thatch roof burned off — already somewhat deteriorated, occupied by one William Mailland. Carrizo functioned as one of the key "major" stations on the line, meaning it offered actual services: coach changes, passenger disembarkation, the mechanical operations that kept the schedule running. The seven major stations west of the Rio Grande bore the weight of an operation that promised mail service between Texas and California in 30 days.

The station's first keeper was William Mailland, and his story carries the darkness that frontier isolation sometimes produces. In May 1858, in what reports described as a drunken fit, Mailland murdered his Native American wife. Fearing revenge from the local Kumeyaay community and arrest by whatever authorities might eventually reach this remote place, he fled. Some believed he died in the desert; others claimed an acquaintance had seen him east of the Colorado River, fleeing south into Sonora. Whether he died alone in the desert or escaped into Mexico, he vanished from the historical record. His victim's name was never recorded in any document that survives.

When the Butterfield Overland Mail took over operations, Carrizo functioned as what the company called a "swing" station — not a major stop but a changing point where fresh horses replaced tired ones. A single hostler managed the livestock and assisted drivers with the team changes that kept the 30-day schedule achievable. The Butterfield Overland Mail shut down in March 1861 as the Civil War reorganized American priorities; the Union Army then used the station as a camp on the road to Fort Yuma and Arizona Territory. Stage service resumed for the Banning and Thomlinson lines from 1867 until 1877, when the railroad's arrival in Fort Yuma made the overland route obsolete.

In 2001, a systematic archaeological investigation of the Carrizo Stage Station site confirmed what the historical record had suggested: two structures and the material remains of the station's operational period from 1857 to 1877. Artifacts documented the everyday life of a remote desert way station — the objects of commerce, cooking, and maintenance that accumulate wherever people live and work. After excavation, the site was reburied and erosion protection installed, preserving what remained for future investigators. The creek still flows most of the year, as it did when Kumeyaay people camped there before the stagecoach ever arrived.