The Neighbors expedition was one of several expeditions sent out to explore the area between San Antonio and El Paso with the purpose of opening a practical wagon road to the west. The more significant expeditions were those led by Col. John C. Hays of the Texas Rangers in 1848, by lieutenants William Henry Chase Whiting and William F. Smith of the United States Army Corps of Engineers in 1849, and by Maj. Robert S. Neighbors, also in 1849. Neighbors, an officer in the Army of the Republic of Texas from 1839 to 1841, was taken prisoner by Mexican general Adrián Woll at San Antonio during the Mexican invasions of 1842. Released in 1844, Neighbors became the Indian agent of Texas, dealing mostly with the Lipan Apache, Tonkawa, and Comanche Indians. Through these experiences he became very familiar with the areas beyond the frontier. Early in 1849 Maj. Gen. William J. Worth, commanding the Eighth Military Department, United States Army at San Antonio, selected Neighbors to lead an expedition to establish an upper route to El Paso. The party left San Antonio, passed through Austin, and then formed up at one of the Torrey Trading Houses near what is now Waco. To accompany him on the expedition, Neighbors selected four Whites: John S. (Rip) Ford, D. C. Sullivan, A. D. Neal, and James Shaw (a celebrated Delaware scout, interpreter, and skillful prairie diplomat)-and four Indians: John Harry (a Delaware), Joe Ellis and Tom Coshatee (Shawnees), and Patrick Goin (a Choctaw). Shaw was put in charge of the Indians. Neighbors also contracted with Buffalo Hump, a Comanche war chief, to guide the party to El Paso. The expedition left the Torrey Trading House on March 23, 1849. Neighbors had Indian agent business at Old Owl's camp, so he traveled northeast up the eastern bank of the Leon River. After several days of delay there, they crossed the Leon and proceeded south to Sanaco's camp on the upper Colorado River, arriving there April 2. The Comanches, always jealous of any indication of possible encroachment on their territory, persuaded Buffalo Hump to disregard his contract and leave the party.
Neighbors then engaged Guadaloupe, the captain of a Comanche band, to guide the expedition on to El Paso. Leaving the Colorado with their new guide on April 5, 1849, the expedition moved ever westward and took the Horsehead Crossing over the Pecos River on April 17. After some considerable difficulty they crossed the northern end of the Davis Mountains, north of the present University of Texas at Austin McDonald Observatory. They struck the Rio Grande on April 25. About a mile before reaching the Rio Grande they came across a trail marked by the tracks of iron-shod horses; there seems to be no doubt that the tracks were from Whiting's party, which from this point had left the valley of the Rio Grande on its return trip. The Neighbors party moved up the east bank of the Rio Grande toward El Paso and arrived there on May 2, 1849. Neighbors felt, however, that the last hundred miles up the Rio Grande were unsuitable for a wagon road. He then chose to return by a more northern route that had been used by the Mexican army between El Paso and the Pecos River. They departed San Elizario on May 6, 1849, by way of Hueco Tanks, Ojo del Alamo, and the Guadalupe Mountains en route to the Pecos. They were guided by a Señor Zambrano. Neighbors reported that the return route from El Paso to the Pecos could serve as a wagon road. He reached Fredericksburg on May 31 and San Antonio on June 2, only eight days after Whiting. His outbound trip to El Paso had taken twenty-three days of actual travel time, but he was able to return to San Antonio in only twenty-one. Neighbors gave a favorable report to Gen. William Selby Harney, who had replaced General Worth. Harney sent out parties to further survey Neighbors's recommendations. His route came to be known as the Upper or Northern route. The Butterfield Overland Mail later ran on this route from the Concho River to El Paso. In the 1990s modern highways and railroads ran over roughly the same routes as the Neighbors outbound and returning trails. The distance from Austin to El Paso was estimated by Ford and Neighbors to be 598 miles, the same distance shown on modern road maps.