Mississippi Highway 69 is a state highway in eastern Mississippi. The route starts at the Alabama state line, and travels northwestward to Columbus. MS 69 then goes through downtown Columbus, and ends at U.S. Route 45 and US 82 in the west side of the town. Before the road was designated as MS 69 in 1941, it was a gravel road from Columbus to the state line. The road was paved in asphalt in 1953. In 1992, US 82 was realigned, and MS 69 was extended through Columbus to its current northern terminus.

Columbus is a city in and the county seat of Lowndes County, on the eastern border of Mississippi, United States, located primarily east, but also north and northeast of the Tombigbee River, which is also part of the Tennessee-Tombigbee Waterway. It is approximately 146 miles (235 km) northeast of Jackson, 92 miles (148 km) north of Meridian, 63 miles (101 km) south of Tupelo, 60 miles (97 km) northwest of Tuscaloosa, Alabama, and 120 miles (193 km) west of Birmingham, Alabama.