Appleton was born on February 14, 1785, in Ipswich, Massachusetts, on a family farm that had been granted to his ancestor, Samuel Appleton, in 1636.^[3] His parents were Samuel Appleton (1738–1819) and Mary (née White) Appleton (d. 1834), daughter of Rev. Timothy White,^[4] and his younger brothers were Timothy Appleton (1778–1857) and Samuel Appleton (1771–1852).^[5]

His paternal grandparents were Elizabeth Sawyer (1709–1785) and Isaac Appleton (1704–1794), the son of Isaac Appleton (1664–1747) and Priscilla Baker, granddaughter of Lt. Gov. Samuel Symonds.^[6] Appleton was also the cousin of U.S. Rep.William Appleton (1786–1862), merchant Samuel Appleton (1766–1853), and U.S. Rep. Nathan Appleton (1779–1861).^[3]

Appleton fought in the War of 1812, commissioned July 3, 1813,^[7] and earned the rank of Lieutenant colonel with the Massachusetts Militia and was later promoted to the rank of Brigadier general.^[8] He commanded actions at Sandy Bay in September 1814 and Gallop's Folly in October 1814.^[7] Appleton lived much of his life in Ipswich, Massachusetts, and nearby Marblehead, Massachusetts, prior to moving to Maine.^[2]

In 1813 and 1814, at the age of 28, Appleton, a practicing lawyer, was elected to represent Gloucester as a Federalist to the Massachusetts legislature where he was an outspoken critic of the Missouri Compromise.^[8] In 1824, he was the official escort of the Marquis de Lafayette upon his visit to Boston.^[5] In 1832, he presented a petition to the Massachusetts legislature prohibiting sales of liquor in fewer quantities than thirty gallons.^[4]

In 1833, he moved to Portland, Maine, and was elected to the Maine House of Representatives^[2] in 1836. The following year, he was chairman of a committee to consider the license system.^[4] In 1837,^[9] he submitted a report on the evils of liquor that became the basis of the Maine Temperance Law of 1846.^[10] The report was considered by Neal Dow to be the first official document in the history of Maine prohibiting the liquor traffic.^[4]

In 1839 and 1840, he was vice president of the American Anti-Slavery Society.^[11]

In the 1842, 1843, and 1844 gubernatorial elections, Appleton ran for Governor of Maine with the Liberty Party, an abolitionist political party.^[11] In 1848, he was a Free Soil presidential elector supporting Martin Van Buren.^[11]

In 1861, during the Civil War, Appleton gave patriotic speeches defending the Union and in support of abolition.^[5]

On November 15, 1807,^[4] he was married to Sarah Fuller (1787–1872), the daughter of Rev. Daniel Fuller and Hannah Bowers, of Gloucester. Together, they were the parents of:^[12][3]

• Samuel Gilman Appleton (1808–1873), who married Sarah Gardiner, daughter of Rev. Sylvester Gardiner, in 1839.^[12]
• Sarah Fuller Appleton (1811–1884), who married Rev. Stephen Caldwell Millett in 1833.^[12]
• James Appleton (1813–1884), who married Sarah Bristol Edwards, daughter of Samuel L. Edwards, in 1842.^[12]
• Mary White Appleton (1815–1905), who did not marry.^[12]
• Elizabeth Putnam Appleton (1818–1897), who married Shelton L. Hall in 1845.^[12]
• Joanna Dodge Appleton (1821–1870), who married Peyton R. Morgan in 1843.^[12]
• Hannah Fuller Appleton (1823–1903), who married Robert Helyer Thayer (1820–1888).^[12]
• Daniel Fuller Appleton (1826–1904), who married Julia Randall (d. 1886), daughter of Nicholas P. Randall. After her death, he married Susan Cowles, daughter of John P. Cowles, in 1889.^[12]
• Harriette Hooper Appleton (1828–1905), who married Rev. John Cotton Smith, rector of St John's Church, Portland, and later of the Church of the Ascension in New York City, in 1849.^[12]
• Anna Whittemore Appleton (1831–); married Dr. Charles H. Osgood, in 1852.^[12]

He lived in Portland from 1833 until 1853 when his elder brother, Timothy Appleton, called him to help manage the family farm in Ipswich.^[6] He retired back to Ipswich, buying out his father's surviving heirs and became the sole owner of Appleton Farm in 1857. He died there in 1862.^[2][3]

Through his son, Daniel, he was the grandfather of 36 including Francis Randall Appleton, a noted New York society man during the Gilded Age.

The Woman's Relief Corps gave a marker on Ipswich's North Green, named in honor of Appleton and in memory of the unknown soldiers and sailors of the Civil War.^[5]