Gallegina was born in 1802 into a leading Cherokee family in their territory. (It is now present-day Georgia.) He was the eldest son of nine children of Uwati and Susanna Reese, who was of mixed Cherokee and European ancestry. When Uwati converted to Christianity, Boudinot took the name of David Uwatie (later he dropped the "u" from his name.) Gallegina's younger brothers were Degataga, better known as Stand Watie, who served with the Confederate Army during the American Civil War and served as Principal Chief (1862-1866); and Thomas Watie. They were the nephews of Major Ridge and cousins of John Ridge.

Gallegina Watie, the Ridges, John Ross, and Charles R. Hicks and his son Elijah Hicks, came to form the ruling elite of the Cherokee Nation in the early nineteenth century. All were of mixed race and had some European-American education; the tribal chiefs had worked to prepare these young men to deal with the United States and its representatives.

Gallegina's Christian education began in 1808, at the age of 6, when Boudinot studied at the local Moravian missionary school. In 1812, he joined the Spring Place school, in what is now Murray County. Around this time, Cherokee leaders were petitioning the government for aid to educate their children, as they wanted to learn aspects of white civilization.

Elias Cornelius, an agent from the American Board of Commissioners for Foreign Missions (ABCFM), came to the community and served to support local education and recruit older students to study in the North. In 1817, the ABCFM opened the Foreign Mission School in Cornwall, Connecticut for educating promising students from foreign, non-Christian cultures, as well as Native American cultures. In 1818, Cornelius selected Gallegina Watie, John Ridge, and a few others to go to the Foreign Mission School. On the journey there, they were introduced to Virginia statesmen Thomas Jefferson and James Monroe.

In Burlington, New Jersey, the young men met Elias Boudinot, president of the American Bible Society and a former member and president of the Second Continental Congress. He and Watie impressed each other, and Watie asked Boudinot for permission to use his name, which he gave. When enrolled at the Foreign Mission School, Watie started using the name Elias Boudinot, which he kept for the rest of his life.

In 1820, Boudinot officially converted to Christianity, attracted to its message of universal love. His Christian belief informed his later work with the Cherokee Nation. In 1824, Boudinot collaborated with others in translating the New Testament into Cherokee and having it printed in the syllabary created by Sequoyah.

While studying in Connecticut, Boudinot met Harriet Ruggles Gold, the daughter of a prominent local family who supported the Foreign Mission School. Her family often invited Boudinot and other Native American students to their home. After Boudinot returned to Cherokee Nation because of illness, he courted Harriet by letter.

His cousin John Ridge also attended the school and in 1824 married a local young woman. This caused considerable controversy in Cornwall, as many townspeople opposed the marriage. After the Ridges' return to New Echota to live, in 1825 the National Council passed a law providing full Cherokee citizenship to children of a Cherokee father and white mother.

In the Cherokee matrilineal kinship culture, children traditionally belonged to the mother's clan and took their status from her people. The Cherokee had long absorbed the mixed-race children of Cherokee mothers and white fathers (usually fur traders). But, the children of Ridge and Boudinot would have had no place in the Cherokee society without the Council's new law, as white women were outsiders and their children would not be considered Cherokee. Historian Theresa Strouth Gaul wrote that the law was inspired by Ridge's marriage and Boudinot's engagement; as the young men were elite Cherokee, it protected the status of their future children.

When Boudinot and Gold first announced their engagement, it was strongly opposed by her family and the Congregational Church. There were also local protests. Gold persisted and finally gained her parents' permission. The couple were married on 28 March 1826 at her home. Local hostility to the marriage, the second between a Cherokee student and a white woman, forced the closing of the Foreign Mission School.

The Boudinots returned to New Echota to live. They had six surviving children: Eleanor Susan; Mary Harriett; William Penn; Sarah Parkhill, Elias Cornelius; and Franklin Brinsmade. Five of the children later married and had families of their own.

Harriet Boudinot died in August 1836, likely of complications from childbirth; she died some months after her seventh child was stillborn.

After his return to New Echota, in 1828 Boudinot was selected by the General Council of the Cherokee as editor for a newspaper, the first to be published by a Native American nation. He worked with a new friend Samuel Worcester, a missionary and printer. Worcester had new type created and cast for the new forms of the Cherokee syllabary. In 1828, the two printed the Cherokee Phoenix in Cherokee and English. While planned as a bi-lingual newspaper, the Phoenix published most of its articles in English; under Boudinot, about 16 percent of the content was published in Cherokee.

The journalist Ann Lackey Landini believes that Boudinot emphasized English in the newspaper because the Cherokee Nation intended it to be a means to explain their people to European Americans and prove they had an admirable civilization. At the same time, the Council intended it to unite the Cherokee through the Southeast. The Phoenix regularly published new laws and other national Cherokee political information in the paper.

Between 1828 and 1832, Boudinot wrote numerous editorials arguing against removal, as proposed by Georgia and supported by President Andrew Jackson. After Congress passed the Indian Removal Act of 1830, federal pressure on the Cherokee increased. Jackson supported removal of the Cherokee and other Southeastern peoples from their eastern homelands to Indian Territory west of the Mississippi in order to make land available for European-American development. Over a roughly four-year period, Boudinot's editorials emphasized that Georgia's disregard of the Constitution and past federal treaties with the Cherokee would not only hurt Cherokee progress in acculturating, but threatened the fabric of the Union. Boudinot's articles recounted the elements of Cherokee assimilation (conversion to Christianity, an increasingly Western-educated population, and a turn toward lives as herdsmen and farmers, etc.) He criticized the "easy" way in which treaty language was distorted by Indian Removal advocates for their own purposes.

In 1832, while on a speaking tour of the North to raise funds for the Phoenix, Boudinot learned that, in Worcester v. Georgia, the US Supreme Court had sustained the Cherokee rights to political and territorial sovereignty within Georgia's borders. He soon learned that President Jackson still supported Indian Removal. In this context, Boudinot began advocating for his people to secure the best possible terms with the US by making a binding treaty of removal, as he believed it was inevitable. His changed position was widely opposed by the Cherokee.

The National Council and John Ross, the Principal Chief, opposed removal, as did the majority of the people. Former allies in the Cherokee government turned against Boudinot and other "treaty advocates," who included John Ridge and Major Ridge. Opponents attacked the men's loyalty and prevented their speaking in councils. Ross denounced Boudinot's "toleration of diversified views in the Cherokee Phoenix and forbade Boudinot from discussing pro-removal arguments in the paper. In protest, Boudinot resigned in the spring of 1832. Ross' brother-in-law, Elijah Hicks, replaced Boudinot as editor.

In 1959, he was inducted into the Georgia Newspaper Hall of Fame in recogniti…

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