La Mesa International offers nonstop service to 17 destinations, served by 14 airlines.
| Destination | Code | Country | Distance | Duration | Airlines |
|---|---|---|---|---|---|
| La Ceiba | LCE | Honduras | 119 km | 0h 40m | |
| Tegucigalpa | TGU | Honduras | 172 km | 0h 45m | H5 |
| Roatan | RTB | Honduras | 177 km | 0h 45m | H5 |
| Belize City | BZE | Belize | 234 km | 1h 0m | 9N |
| San Salvador | SAL | El Salvador | 253 km | 0h 50m | AV |
| Guatemala City | GUA | Guatemala | 295 km | 1h 0m | 5U, H5 |
| Panama City | PTY | Panama | 1,166 km | 2h 13m | CM |
| Mexico City | MEX | Mexico | 1,262 km | 2h 25m | AM |
| Miami | MIA | USA | 1,394 km | 2h 26m | AA, N3, F9 |
| Fort Lauderdale | FLL | USA | 1,426 km | 2h 19m | NK, B6 |
| Orlando | MCO | USA | 1,590 km | 2h 44m | NK, F9 |
| New Orleans | MSY | USA | 1,626 km | 2h 31m | NK |
| Houston | IAH | USA | 1,778 km | 2h 58m | UA, F9 |
| Atlanta | ATL | USA | 2,044 km | 3h 17m | DL, F9 |
| New York | EWR | USA | 3,096 km | 4h 19m | UA |
| New York | JFK | USA | 3,108 km | 4h 31m | B6 |
| Madrid | MAD | Spain | 8,441 km | 9h 55m | UX |