After the war he went to California, where he reportedly died of a fall from his mount due to starvation near Clear Lake on 25 February 1850, following a cross-country expedition which fixed the location of Humboldt Bay.

[2] Because of his failing health, Gregg followed his doctor's recommendation and traveled alongside a merchant caravan to Santa Fe, New Mexico on a trail beginning at Van Buren, Arkansas, in 1831.

[3] By 1840, Gregg had learned Spanish, crossed the plains between Missouri and Santa Fe four times, traveled the Chihuahua Trail into Mexico, and become a successful businessman.

[2] In March the caravan was attacked by Pawnee near Trujillo Creek in Oldham County, Texas, and a storm scattered most of his stock across the Llano Estacado, but the group continued eastward through Indian Territory to Fort Smith and Van Buren.

[5] Gregg's book Commerce of the Prairies, published in two volumes in 1844, is an account of his time spent as a trader on the Santa Fe Trail from 1831 to 1840 and includes commentary on the geography, botany, geology, and culture of New Mexico.

[2] The map he produced of the Santa Fe Trail and surrounding plains was the most detailed up to that time, and his suggestions of where the Red River headwaters might be found inspired the journey of Randolph B. Marcy and George B. McClellan in 1852.

[8] As part of his equipment for his trip to Santa Fe with the Owens wagon train were special-sized plates for his sixth-plate camera, probably delivered to him by naturalist Friedrich Adolph Wislizenus.

[1] Gregg left Owens' caravan at the outbreak of the Mexican–American War when he joined General John E. Wool's Arkansas Volunteers as an unofficial news correspondent and interpreter.

[10] Gregg traveled to Washington, D.C., where he was unimpressed after meeting President James K. Polk, and took a series of steamships down the Mississippi River into the Gulf of Mexico, then up the Rio Grande and back to Saltillo at the end of 1847.

[2][7][11] In 1849, Gregg joined the California Gold Rush by sailing from Mazatlán to San Francisco, eating canned food for the first time and remarking in a letter that he liked it.

B. Truesdale of Oregon; Charles C. Southard of Boston; Isaac Wilson of Missouri; Lewis Keysor Wood of Kentucky; and James Van Duzen.

[14] A few days past the start, David A. Buck discovered the South Fork Trinity River, where the party encountered a group of Indians who fled from them.

[14] Leaving Trinidad, they crossed a large river, but the fed-up members of the exploring party did not wish to wait for Gregg to determine the latitude of the mouth, and so pushed off without him.

Finding the country much broken along the coast, making it continually necessary to cross abrupt points, and deep gulches and canyons, after struggling along for several days, they concluded to abandon that route and strike easterly toward the Sacramento valley.

Other reports say he died on February 25 near Clear Lake, California, of poor health and the hardships of his journey,[20] while another casts doubt on the story that his companions buried him, instead suggesting he survived at least briefly at an Indian village.

[2] The Gregg party's trip triggered an 1850 expedition by Colonel Redick McKee to create treaties with Northern California Indians, which were never ratified.