Greenville-Spartanburg International offers nonstop service to 58 destinations, served by 7 airlines.
| Destination | Code | Country | Distance | Duration | Airlines |
|---|---|---|---|---|---|
| Charlotte | CLT | USA | 122 km | 1h 15m | AA |
| Atlanta | ATL | USA | 247 km | 1h 6m | DL |
| Nashville | BNA | USA | 426 km | 1h 20m | WN |
| Cincinnati | CVG | USA | 510 km | 1h 21m | MX |
| Columbus | CMH | USA | 569 km | 1h 25m | MX |
| Dulles | IAD | USA | 619 km | 1h 36m | UA |
| Washington | DCA | USA | 637 km | 1h 43m | AA |
| Pittsburgh | PIT | USA | 645 km | 1h 27m | MX |
| Orlando | SFB | USA | 684 km | 1h 25m | G4 |
| Baltimore | BWI | USA | 685 km | 1h 30m | WN |
| Orlando | MCO | USA | 721 km | 1h 37m | MX |
| Tampa | TPA | USA | 766 km | 1h 39m | MX |
| Saint Petersburg | PIE | USA | 775 km | 1h 34m | G4 |
| Detroit | DTW | USA | 818 km | 1h 51m | DL |
| Philadelphia | PHL | USA | 828 km | 1h 53m | AA |
| Sarasota | SRQ | USA | 832 km | 1h 38m | G4 |
| Fort Myers | RSW | USA | 928 km | 1h 48m | MX |
| Chicago | ORD | USA | 929 km | 2h 20m | AA, UA |
| New York | EWR | USA | 956 km | 2h 6m | UA |
| New York | LGA | USA | 982 km | 2h 1m | AA, DL |
| Fort Lauderdale | FLL | USA | 997 km | 1h 58m | G4, MX |
| Miami | MIA | USA | 1,025 km | 1h 58m | AA |
| New Haven | HVN | USA | 1,080 km | 1h 59m | XP |
| Hartford | BDL | USA | 1,140 km | 2h 5m | MX |
| Providence | PVD | USA | 1,208 km | 2h 2m | MX |
| Houston | IAH | USA | 1,347 km | 2h 49m | UA |
| Dallas | DFW | USA | 1,387 km | 2h 56m | AA |
| Denver | DEN | USA | 2,057 km | 3h 36m | UA |
| Los Angeles | LAX | USA | 3,310 km | 5h 6m | MX |