The town was in former times a major port, but is now a semi-ghost town as a result of the decline of the river trade. During the American Civil War, it was used by U.S. Grant as a supply hub, but his military occupation of the town diverted much trade towards Chicago and Cairo could never quite get it back.
- US 51. Head south on US Highway 51 from Interstate 57.
- 1 Cairo Regional Airport (CIR IATA) (4 mi (6.4 km) northwest of town on the other side of the interstate.).
- 1 Cairo Custom House Museum, ☏ . 14th and Washington Ave. An American Civil War and local history museum. M-F 10AM-12PM, 1PM-3PM.
- 2 Fort Defiance State Park. This once neglected state park has come back into better days thanks to local efforts. It looks out over the Ohio and Mississippi rivers as the two powerful water flows attempt to combine.
- Safford Memorial Library, 1609 Washington Ave, ☏ . M-F 10AM-5PM, Sa 9AM-12PM. Home to Civil War documents, antiques, and paintings.
- 3 Magnolia Manor, 2700 Washington Ave., ☏ .
- Levee Footrace, ☏ . A 5000 and 10,000 meter run held on the Mississippi River Levee is held the second Saturday of November.
- St Mary's Park. This city park once played host to Theodore Roosevelt, but now hosts the city's residents with recreation facilities.
- Andy's Drive-In, ☏ .
- Cairo Truck Stop, ☏ .
- Chris's Cafe, ☏ .
- Dairy Hut, ☏ .
- Mack's Barbecue, ☏ .
- Nonny's, ☏ . 2203 Sycamore.
- Nu Diner, 300 Washington Ave, ☏ .
- Belvedere Motel, 3901 Sycamore St, ☏ .
- Days Inn, ☏ . I-57 and US 51.
- Garden Inn Motel, ☏ . US 51.
- Relax Inn, 214 Washington Ave, ☏ .
|Routes through Cairo|
|Effingham ← Marion ← Jct to Metropolis ←||N S||→ Sikeston → END|
|Carbondale ← Cobden ←||N S||→ Memphis → Jackson|
|Springfield ← Sikeston ←||W E||→ Paducah → Evansville/Elizabethtown|
|East St. Louis ← Cahokia ← Jct W ←||N S||→ END|