Charleston Afb International offers nonstop service to 55 destinations, served by 13 airlines.
| Destination | Code | Country | Distance | Duration | Airlines |
|---|---|---|---|---|---|
| Charlotte | CLT | USA | 271 km | 1h 15m | AA |
| Atlanta | ATL | USA | 419 km | 1h 18m | DL |
| Orlando | MCO | USA | 508 km | 1h 28m | MX |
| Norfolk | ORF | USA | 566 km | 1h 19m | MX |
| Richmond | RIC | USA | 569 km | 1h 20m | MX |
| Tampa | TPA | USA | 594 km | 1h 29m | MX |
| West Palm Beach | PBI | USA | 687 km | 1h 38m | MX |
| Nashville | BNA | USA | 707 km | 1h 35m | WN |
| Dulles | IAD | USA | 712 km | 1h 37m | UA |
| Washington | DCA | USA | 715 km | 1h 43m | AA |
| Fort Myers | RSW | USA | 723 km | 1h 46m | MX |
| Fort Lauderdale | FLL | USA | 755 km | 1h 38m | B6, NK, MX |
| Baltimore | BWI | USA | 761 km | 1h 35m | WN |
| Louisville | SDF | USA | 781 km | 1h 52m | MX |
| Miami | MIA | USA | 786 km | 1h 46m | AA |
| Cincinnati | CVG | USA | 801 km | 1h 43m | G4, MX |
| Columbus | CMH | USA | 829 km | 1h 44m | MX |
| Pittsburgh | PIT | USA | 844 km | 1h 46m | MX |
| Atlantic City | ACY | USA | 878 km | 1h 45m | MX |
| Philadelphia | PHL | USA | 886 km | 1h 53m | AA, F9 |
| Akron | CAK | USA | 899 km | 1h 52m | MX |
| Indianapolis | IND | USA | 943 km | 1h 55m | G4 |
| New York | EWR | USA | 1,011 km | 2h 0m | UA, NK |
| New Orleans | MSY | USA | 1,022 km | 2h 8m | MX |
| New York | JFK | USA | 1,025 km | 2h 3m | B6, DL |
| New York | LGA | USA | 1,033 km | 2h 2m | DL, AA |
| Westchester County | HPN | USA | 1,068 km | 2h 9m | MX |
| Islip | ISP | USA | 1,072 km | 1h 54m | MX |
| Detroit | DTW | USA | 1,075 km | 2h 9m | DL |
| Newburgh | SWF | USA | 1,090 km | 2h 8m | MX |
| New Haven | HVN | USA | 1,125 km | 2h 7m | XP, MX |
| Saint Louis | STL | USA | 1,137 km | 2h 15m | WN |
| Rochester | ROC | USA | 1,155 km | 2h 14m | MX |
| Syracuse | SYR | USA | 1,186 km | 2h 9m | MX |
| Hartford | BDL | USA | 1,195 km | 2h 6m | MX |
| Chicago | MDW | USA | 1,199 km | 2h 15m | WN |
| Toronto | YYZ | Canada | 1,199 km | 2h 14m | AC |
| Albany | ALB | USA | 1,223 km | 2h 12m | MX |
| Chicago | ORD | USA | 1,224 km | 2h 37m | AA, UA |
| Providence | PVD | USA | 1,241 km | 2h 8m | MX |
| Boston | BOS | USA | 1,317 km | 2h 24m | B6, DL |
| Manchester | MHT | USA | 1,345 km | 2h 20m | MX |
| Burlington | BTV | USA | 1,417 km | 2h 28m | MX |
| Portland | PWM | USA | 1,464 km | 2h 25m | MX |
| Cancun | CUN | Mexico | 1,476 km | 2h 50m | MX |
| Houston | IAH | USA | 1,488 km | 2h 55m | UA |
| Houston | HOU | USA | 1,493 km | 2h 40m | WN |
| Kansas City | MCI | USA | 1,498 km | 2h 25m | WN |
| Dallas | DAL | USA | 1,571 km | 2h 43m | WN |
| Dallas | DFW | USA | 1,588 km | 3h 9m | AA |
| Austin | AUS | USA | 1,698 km | 3h 0m | WN |
| Minneapolis | MSP | USA | 1,750 km | 3h 4m | DL, SY |
| Denver | DEN | USA | 2,333 km | 4h 3m | WN, UA |
| Los Angeles | LAX | USA | 3,550 km | 5h 43m | MX |
| Seattle | SEA | USA | 3,886 km | 6h 3m | AS |