Key West International offers nonstop service to 48 destinations, served by 7 airlines.
| Destination | Code | Country | Distance | Duration | Airlines |
|---|---|---|---|---|---|
| Miami | MIA | USA | 202 km | 0h 53m | AA |
| Saint Petersburg | PIE | USA | 383 km | 1h 5m | G4 |
| Tampa | TPA | USA | 387 km | 1h 10m | MX |
| Orlando | MCO | USA | 432 km | 1h 18m | MX |
| Orlando | SFB | USA | 470 km | 1h 12m | G4 |
| Atlanta | ATL | USA | 1,040 km | 2h 6m | DL |
| Charlotte | CLT | USA | 1,184 km | 2h 25m | AA |
| Asheville | AVL | USA | 1,208 km | 2h 8m | G4 |
| Knoxville | TYS | USA | 1,265 km | 2h 15m | G4 |
| Raleigh/Durham | RDU | USA | 1,286 km | 2h 21m | MX |
| Houston | IAH | USA | 1,472 km | 3h 8m | UA |
| Cincinnati | CVG | USA | 1,631 km | 2h 47m | G4 |
| Washington | DCA | USA | 1,646 km | 2h 53m | AA |
| Dulles | IAD | USA | 1,647 km | 2h 49m | UA |
| Columbus | LCK | USA | 1,696 km | 2h 46m | G4 |
| Indianapolis | IND | USA | 1,734 km | 2h 55m | G4 |
| Dallas | DFW | USA | 1,753 km | 3h 22m | AA |
| Pittsburgh | PIT | USA | 1,773 km | 2h 48m | G4 |
| Philadelphia | PHL | USA | 1,805 km | 3h 7m | AA |
| New York | EWR | USA | 1,923 km | 3h 9m | UA |
| New York | LGA | USA | 1,942 km | 3h 19m | AA, DL |
| Chicago | ORD | USA | 2,014 km | 3h 50m | AA, UA |
| New Haven | HVN | USA | 2,027 km | 3h 13m | XP |
| Boston | BOS | USA | 2,209 km | 3h 34m | AA, B6 |