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Palmyra is situated on a natural rock formation about seven miles west of the Mississippi River. When European settlers came to the area in the early 1800s, the site had already been a Sac and Fox campsite for several years. Among the first settlers were Benjamin Vanlandingham and his family, who came from Kentucky, building a log cabin near Big Spring in 1818. Palmyra was platted as the county seat in 1819, and named for the biblical city. In 1825, Palmyra was chosen to be the first land office in northeastern Missouri, and as the Marion County seat in 1826. The Hannibal & St. Joseph Railroad extended its track to the town in 1857, and the Palmyra & Quincy Railroad came in 1860. During the American Civil War, Plamyra and Marion County were sharply divided in their loyalties. In 1862, Confederate Colonel Joseph E. Porter raided the town, releasing prisoners who were being held in the Marion County jail, and capturing Andrew Allsman, a Union sympathizer charged with betraying neighbors sympathetic with the Confederacy. Union Colonel John McNeil demanded the return of Allsman. Reportedly, Porter released Allsman with an escort to see him safely to a road leading to Palmyra, but Allsman was never seen again. In retaliation, McNeil ordered the execution of ten Confederate prisoners on October 18, 1862, an act that became known as the Palmyra Massacre, while McNeil was denounced in newspapers, in the Union states as well as in the South, as the Butcher of Palmyra. Today, several antebellum buildings remain in Palmyra, individually listed on the National Register of Historic Places. Palmyra is accessed by US Highway 24, which is also Highway 61. South River and Huiskamp are northeast of Palmyra, while Woodland is southwest.

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