Samuel Austin Worcester (January 19, 1798 – April 20, 1859) was an American missionary to the Cherokee, translator of the Bible, printer, and defender of the Cherokee sovereignty. He collaborated with Elias Boudinot (Cherokee) in Georgia to establish the Cherokee Phoenix, the first Native American newspaper, which was printed in both English and the Cherokee syllabary. The Cherokee gave Worcester the honorary name A-tse-nu-sti, which translates to "messenger" in English.

Worcester was arrested in Georgia and convicted for disobeying the state's law restricting white missionaries from living in Cherokee territory without a state license. On appeal, he was the plaintiff in Worcester v. Georgia (1832), a case that went to the United States Supreme Court. The court held that Georgia's law was unconstitutional. Chief Justice John Marshall defined in his dicta that the federal government had an exclusive relationship with the Indian nations and recognized the latter's sovereignty, above state laws. Both President Andrew Jackson and Governor George Gilmer ignored the ruling.

After receiving a pardon from the subsequent governor, Worcester left Georgia on a promise to never return. He moved to Indian Territory in 1836 in the period of Cherokee removal on the Trail of Tears. His wife died there in 1839. Worcester resumed his ministry, and continued translating the Bible into Cherokee. He established the first printing press in that part of the United States, working with the Cherokee to publish their newspaper in Cherokee and English. In 1963, he was inducted into the Hall of Great Westerners of the National Cowboy & Western Heritage Museum.

Worcester is a character in Unto These Hills, an outdoor drama that has been performed in Cherokee, NC since 1950.

Worcester was born in Peacham, Vermont, on January 19, 1798, to the Rev. Leonard Worcester, a minister and his wife. His father was the seventh generation of pastors in his family, dating to ancestors who lived in England. According to Charles Perry of the Peacham Historical Association, the father Leonard Worcester also worked as a printer in the town. The young Worcester attended common schools and studied printing with his father. In 1819, he graduated with honors from the University of Vermont.

Samuel Worcester became a Congregational minister and decided to become a missionary. After graduating from Andover Theological Seminary in 1823, he expected to be sent to India, Palestine, or the Hawaii. Instead, the American Board of Commissioners for Foreign Missions (ABCFM) sent him to the American Southeast to minister to the local Native American tribes.

Worcester married Ann Orr of Bedford, New Hampshire, whom he had met at Andover. They moved to Brainerd Mission, where he was assigned as a missionary to the Cherokee in August 1825. The goals ABCFM set for them were, "...make the whole tribe English in their language, civilized in their habits and Christian in their religion." Other missionaries working among the Cherokee had already learned that they first needed to learn the Cherokee language. While living at Brainerd, the Worcesters had their first child, a daughter. Two years later, they moved to New Echota, established in 1825 as the capital of the nation on the headwaters of Oostanaula River in what is now Georgia. Worcester worked with Elias Boudinot (Cherokee) to establish the Cherokee Phoenix newspaper, the first published by a Native American nation. It was published in Cherokee, using the syllabary developed by Sequoyah, and in English.

The Worcesters had seven children together: Ann Eliza, Sarah, Jerusha, Hannah, Leonard, John Orr and Mary Eleanor. Ann Eliza followed her father in becoming a missionary. With her husband, William Schenck Robertson, she founded Nuyaka Mission in the Indian Territory.