[3] Marysville was laid out in 1855 by Francis J. Marshall, and designated in that same year the county seat.

British explorer Richard Francis Burton en route to California in 1860 noted: "Passing by Marysville, in old maps Palmetto City, a country-town which thrives by selling whiskey to ruffians of all descriptions ..."[5] The old Pony Express Station still stands in downtown Marysville.

[6] In Beyond the Mississippi (1867), Albert D. Richardson, who passed through Marysville in 1860, wrote that the town—which was named after the Border Ruffian Marshall's wife—"had 50 houses and was famed for whisky and shooting affrays.

"[7] Marysville owed much of its prosperity to the Union Pacific Railroad, which became a major employer.

But as the city grew along the railroad most of the community was across the tracks from a good part of downtown.

As rail traffic increased, vehicular delays were estimated at 7.5 to 8 hours per day at the five grade crossings, which also affected emergency vehicles.

In 2006 the main line was moved out of the center of town to a bypass to the south and west, with grade separations for US-36 and US-77.

[9] Marysville is located in northeastern Kansas near the Nebraska border, approximately 75 miles (120 km) northwest of the Kansas capital of Topeka and 67 miles (108 km) south of Lincoln, Nebraska.

[10] The 2020 United States census counted 3,447 people, 1,458 households, and 841 families in Marysville.

37.4% of households consisted of individuals and 17.4% had someone living alone who was 65 years of age or older.

38.1% of all households were made up of individuals, and 18.1% had someone living alone who was 65 years of age or older.

The community is served by Marysville USD 364 public school district.