In 1863, "Buffalo" Bill Mathewson opened a trading post next to Cow Creek Crossing. His hand-dug, 34 foot deep, stone-lined well that served the U.S. Calvary and Santa Fe Trail travelers has been preserved at this site. It is believed that the well was named after Mathewson after his heroic deeds in saving lives during Indian attacks in the area. One cowhand on the early ranch was young Bill Cody.

In a early reference to Cow Creek Crossing, eighteen-year-old Susan Shelby Magoffin, first Anglo lady to travel the Santa Fe Trail, wrote in her diary July 2, 1846: "Camped tonight at big Cow Creek, three miles from the other which we left at seven o'clock. The crossing here is very bad and took us till moon down to cross. It is good water and wood, so we struck camp."

Commercial use of the Santa Fe Trail closed in Kansas in 1872, having been replaced by the railroad.