• Colonel of the U.S. Army James Gadsden, 1788
• Treaty of Payne's Landing, 1832

Gadsden next decided to leave the U.S. Army, and he was appointed as a commissioner in 1823, to help with the organization and the illegal expulsion of most of the Seminole Indian Tribe from their homes in Florida and southern Georgia, along the Trail of Tears to land reservations that had been set aside for them in bleak and inhospitable Oklahoma.

Years later Gadsden County, Florida, was named in his honor, and also the city of Gadsden, Alabama, and the town of Gadsden, Arizona.

Later Gadsden served as the president of the South Carolina Railroad company from 1840 to 1850. In this role, Gadsden and his associates decided to promote the construction of a transcontinental railroad from the Atlantic and Pacific Oceans. This railroad would hypothetically have been by way of the southern route from Georgia through Alabama, Mississippi, Louisiana, and Texas to El Paso, Texas, and then through the newly acquired American land that would decades later become New Mexico and Arizona. Finally, after crossing the Colorado River into California, it would have crossed the Mojave Desert and the mountains to the seaport city of San Diego, California.

After a lot of surveying work had been done in the Southwest, it was decided that a railroad across the land that later became central New Mexico and central Arizona would be infeasible. Also, much of the boundary between the United States and Mexico had been left unreasonably vague by the Treaty of Guadalupe Hidalgo that had been signed and ratified by the United States and Mexico in 1848.

Gadsden had supported nullification in 1831. In 1850 he advocated secession by South Carolina when California was admitted to the Union as a free state. Gadsden considered slavery “a social blessing” and abolitionists “the greatest curse of the nation.”

When the secession proposal failed, Gadsden, working with his cousin Isaac Edward Holmes, a lawyer in San Francisco since 1851, and the California state senator Thomas Jefferson Green, attempted to divide California in two. They proposed that the southern half would allow slavery. Gadsden planned to establish a slave holding colony there based on rice, cotton and sugar. He would use slave labor to build a railroad and highway, originating in either San Antonio or on the Red River, that would transport people to the California gold fields. Toward this end, on December 31, 1851, Gadsden asked Green to secure from the California state legislature a large land grant located between the 34th and 36th parallels; it would eventually serve as the dividing line for the two California states.

A few months after this, Gadsden and 1,200 potential settlers from South Carolina and Florida submitted a petition to the California legislature for permanent citizenship and permission to establish a rural district that would be farmed by "not less than Two Thousand of their African Domestics". The petition stimulated some debate, but it finally died in committee.

In 1853, Gadsden was appointed by the U.S. Government as the new American minister to Mexico, with instructions to purchase more land from Mexico for the prospective railroad route across southernmost New Mexico and Arizona, and to clear up the possibility of disputes over the location of the boundary between the two countries.

Gadsden successfully carried out this mission by negotiating with the Mexican government in Mexico City for the purchase of more land from Mexico for southern most New Mexico and Arizona, and by establishing the boundary between the United States and Mexico as two long line segments between the Rio Grande at the westernmost tip of Texas all the way to the Colorado River at the eastern boundary of California. This treaty is called the "Gadsden Treaty", and it led to the Gadsden Purchase from Mexico of about 30,000 square miles (78,000 km²) of land in northernmost Mexico for $10,000,000.

As events unfolded in the following decades, and well over a century, the dreamed-up railroad just to the north of the Mexican border was never built. However, the land bought in the Gadsden Purchase later contained the site of Arizona's second largest city, Tucson, the minor cities and towns of Casa Grande and Yuma, Arizona, Lordsburg and Deming, New Mexico, and it cleared up the status of the area north of the Gila River, that later became the metropolitan area of Phoenix, Scottsdale, Mesa, Glendale and Tempe, Arizona.

When it comes to the land well south of Phoenix where tentative plans had been made to build a transcontinental railroad, most of this is arid desert land that is not suitable for much human habitation. Nearly all of this Federally owned land was, in the long run, set aside as a large, sparsely inhabited American Indian reservation, testing and combat practicing ranges for the U.S. Air Force, the large Organ Pipe Cactus National Monument and Cabeza Prieta National Wildlife Refuge, the Coronado National Forest, the Sonoran Desert National Monument, the Ironwood Forest National Monument, the Saguaro National Park, and the Fort Huachuca Military Reservation of the U.S. Army.

Gadsden was buried in St. Philips Church Cemetery in Charleston, South Carolina.

By the Treaty of Moultrie Creek in 1823, the Seminoles had relinquished all claims to land in the Florida Territory in return for a reservation in the center of the Florida peninsula and certain payments, supplies and services to be provided by the U.S. government, guaranteed for twenty years. After the election of Andrew Jackson as President of the United States in 1828, the movement to transfer all Indians in the United States to west of the Mississippi River grew, and in 1830 the United States Congress passed the Indian Removal Act.

Determined to move the Seminoles west, the United States Department of War appointed James Gadsden to negotiate a new treaty with them. In the spring of 1832 the Seminoles on the reservation were called to a meeting at Payne's Landing on the Oklawaha River. The negotiations were conducted in obscurity, if not secrecy. No minutes were taken, nor were any detailed accounts of the negotiations ever published. This was to lead to trouble later.

The U.S. government wanted the Seminoles to move to the Creek Reservation in what was then part of the Arkansas Territory (which later became part of the Indian Territory), to become part of the Creek Nation, and to return all runaway slaves to their lawful owners. None of these demands were agreeable to the Seminoles. They had heard that the climate at the Creek Reservation was harsher than in Florida. The Seminoles of Florida did not consider themselves part of the Creeks. Although many of the groups in Florida had come from what whites called Creek tribes, they did not feel any connection. Some of the groups in Florida, such as the Choctaws, Yamasees and the Yuchis had never been grouped with the Creeks. Finally, runaway slaves, while often held as slaves by the Seminoles (under much milder conditions than with whites), were fairly well integrated into the bands, often inter - marrying, and rising to positions of influence and leadership.

The treaty negotiated at Payne's Landing called for the Seminoles to move west if the land were found to be suitable. The delegation of seven chiefs who were to inspect the new reservation did not leave Florida until October 1832. After touring the area for several months and conferring with the Creeks who had already been settled there, the seven chiefs signed on March 28, 1833 at Fort Gibson, Arkansas Territory, a statement that the new land was acceptable. Upon their return to Florida, however, most of the chiefs renounced the statement, claiming that they had not signed it, or that they had been forced to sign it, and in any case, that they did not have the power to decide for all the tribes and bands that resided on the reservation. Even some U.S. Army officers observed that the chiefs "had been wheedled and bullied into signing." Furthermore, "there is evidence of trickery by the whites in the way the treaty is phrased."

Several villages had been allowed to stay in the area of the Apalachicola River after 1823 when the rest of the Seminoles had been forced into the new reservation. Gadsden was able to persuade the chiefs of these villages to move, however, and they went west in 1834. The United States Senate finally ratified the Treaty of Payne's Landing in April 1834.

The treaty had given the Seminoles three years to move west of the Mississippi. The government interpreted the three years as starting in 1832, and expected the Seminoles to move in 1835. Fort King, in what is now Ocala was reopened in 1834. A new Seminole agent, Wiley Thompson, was appointed in 1834, and the task of persuading the Seminoles to move fell to him. He called the chiefs together at Fort King in October 1834 to talk to them about the removal to the west. The Seminoles informed Thompson that they had no intention of moving, and that they did not feel bound by the Treaty of Payne's Landing. Thompson then requested reinforcements for Fort King and Fort Brooke, reporting that, "the Indians after they had received the Annuity, purchased an unusually large quantity of Powder & Lead." Brigadier General Duncan L. Clinch, United States Army commander for Florida, also warned Washington that the Seminoles did not intend to move, and that more troops would be needed to force them to move. In March 1835 Thompson called the chiefs together to read a letter from Andrew Jackson to them. In his letter, Jackson said, "Should you ... refuse to move, I have then directed the Commanding officer to remove you by force." The chiefs asked for thirty days to respond. A month later the Seminole chiefs told Thompson that they would not move west. Thompson and the chiefs began arguing, and General Clinch had to intervene to prevent bloodshed. Eventually, eight of the chiefs agreed to move west, but asked to delay the move until the end of the year, and Thompson and Clinch agreed.

Five of the most important of the Seminole chiefs, including Micanopy of the Alachua Seminoles, had not agreed to the move. In retaliation, Thompson declared that those chiefs were removed from their positions. As relations with the Seminoles deteriorated, Thompson forbade the sale of guns and ammunition to the Seminoles. Osceola, a young warrior beginning to be noticed by the whites, was particularly upset by the ban, feeling that it equated Seminoles with slaves and said, "The white man shall not make me black. I will make the white man red with blood; and then blacken him in the sun and rain ... and the buzzard live upon his flesh." In spite of this, Thompson considered Osceola to be a friend, and gave him a rifle. Later, though, when Osceola was causing trouble, Thompson had him locked up at Fort King for a night. The next day, in order to secure his release, Osceola agreed to abide by the Treaty of Payne's Landing and to bring his followers in.

The situation grew worse. In August 1835 Private Kinsley Dalton (for whom Dalton, Georgia is named) was killed by Seminoles as he was carrying the mail from Fort Brooke to Fort King. In November Chief Charley Emathla, wanting no part of a war, led his people towards Fort Brooke where they were to board ships to go west. This was considered a betrayal by other Seminoles. Osceola met Charlie Emathla on the trail and killed him. The Second Seminole War was beginning.

Signatories:

• James Gadsden
• Holati Emartla, his x mark
• Jumper, his x mark
• Fuch-ta-lus-ta-Hadjo, his x mark
• Charley Emartla, his x mark
• Coa Hadjo, his x mark
• Ar-pi-uck-i, or Sam Jones, his x mark
• Ya-ha Hadjo, his x mark
• Mico-Noha, his x mark
• Tokose-Emartla, or Jno. Hicks. his x mark
• Cat-sha-Tusta-nuck-i, his x mark
• Hola-at-a-Mico, his x mark (aka Billy Bowlegs)
• Hitch-it-i-Mico, his x mark
• E-ne-hah, his x mark
• Ya- ha- emartla Chup- ko, his mark
• Moke-his-she-lar-ni, his x mark

Witnesses:

• Douglas Vass, Secretary to Commissioner,
• John Phagan, Agent,
• Stephen Richards, Interpreter,
• Abraham, Interpreter, his x mark,
• Cudjo, Interpreter, his x mark,
• Erastus Rogers,
• B. Joscan.