| 1 | GUA to PDX Portland, United States | 2,838 mi | ~6h 26m | American Airlines | 2×/wk |
| 2 | GUA to SFO San Francisco, United States | 2,515 mi | ~5h 46m | Avianca | 3×/wk |
| 3 | GUA to LAX Los Angeles, United States | 2,194 mi | ~5h 7m | Alaska Airlines, United Airlines, and Volaris Costa Rica | 3-4/day |
| 4 | GUA to EWR Newark, United States | 2,055 mi | ~4h 49m | United Airlines | 1/day |
| 5 | GUA to ORD Chicago, United States | 1,899 mi | ~4h 30m | United Airlines and American Airlines | 3×/wk |
| 6 | GUA to IAD Washington, United States | 1,862 mi | ~4h 25m | United Airlines | 1/day |
| 7 | GUA to SDQ Santo Domingo, Dominican Republic | 1,406 mi | ~3h 29m | Arajet | 1/day |
| 8 | GUA to ATL Atlanta, United States | 1,371 mi | ~3h 25m | Delta Air Lines | 1-2/day |
| 9 | GUA to DFW Dallas, United States | 1,330 mi | ~3h 20m | American Airlines and Frontier Airlines | 1-2/day |
| 10 | GUA to BOG Bogota, Colombia | 1,307 mi | ~3h 17m | Avianca and Copa Colombia | 2-3/day |
| 11 | GUA to MCO Orlando, United States | 1,124 mi | ~2h 54m | Frontier Airlines | 2×/wk |
| 12 | GUA to IAH Houston, United States | 1,107 mi | ~2h 52m | United Airlines | 3/day |
| 13 | GUA to FLL Fort Lauderdale, United States | 1,039 mi | ~2h 44m | JetBlue Airways | 1/day |
| 14 | GUA to MIA Miami, United States | 1,019 mi | ~2h 41m | American Airlines | 2-3/day |
| 15 | GUA to PTY Panama City, Panama | 844 mi | ~2h 19m | Copa | 5-6/day |
| 16 | GUA to MEX Mexico City, Mexico | 656 mi | ~1h 56m | Aeromexico, Volaris, and Volaris Costa Rica | 3-4/day |
| 17 | GUA to SJO San Jose, Costa Rica | 531 mi | ~1h 41m | Avianca and Copa | 3/day |
| 18 | GUA to CUN Cancun, Mexico | 506 mi | ~1h 38m | Volaris and Avianca | 1-2/day |
| 19 | GUA to MGA Managua, Nicaragua | 338 mi | ~1h 17m | Copa | 3×/wk |
| 20 | GUA to SAP La Mesa, Honduras | 184 mi | ~58m | Thomas Cook Balearics | 1/day |
| 21 | GUA to FRS San Benito, Guatemala | 167 mi | ~56m | Avianca | 3/day |
| 22 | GUA to SAL Santa Clara, El Salvador | 126 mi | ~51m | Avianca and Iberia | 5-6/day |