Although Coronado's exact route across the plains is uncertain and has been widely disputed, his men and he are thought to have camped near the present location of Lyons on their quest for Quivira, a Native American place that Indians to the southwest had told them was fabulously wealthy in gold.

West of Lyons is a cross commemorating Juan de Padilla, a member of Coronado's expedition, who returned the following year as a missionary.

He was killed in 1542 by Native Americans after establishing a church in the area, and is considered the first Christian martyr in North America.

[4] In 1803, most of modern Kansas was secured by the United States as part of the Louisiana Purchase.

Lyons Main Street (U.S. Highway 56) is based on the Santa Fe Trail.

[7] The line was leased and operated by the Atchison, Topeka and Santa Fe Railway.

[8] In 1992, the line from Marion to McPherson was sold to Central Kansas Railway.

In 1993, after heavy flood damage, the line from Marion to McPherson was abandoned.

The original branch line connected Florence, Marion, Canada, Hillsboro, Lehigh, Canton, Galva, McPherson, Conway, Windom, Little River, Mitchell, Lyons, Chase, and Ellinwood.

[11][12] In the 1970s, the federal government was interested in using a local site for the burial of high-level nuclear waste.

[13] According to the United States Census Bureau, the city has a total area of 2.36 square miles (6.11 km2), all land.

[15] The 2020 United States census counted 3,611 people, 1,462 households, and 946 families in Lyons.

30.3% of households consisted of individuals and 14.1% had someone living alone who was 65 years of age or older.

32.1% of all households were made up of individuals, and 16.4% had someone living alone who was 65 years of age or older.

The community is served by Lyons USD 405 public school district.