| 1 | PIT to LHR London, United Kingdom | 3,710 mi | ~8h 14m | British Airways | 1/day |
| 2 | PIT to DUB Dublin, Ireland | 3,435 mi | ~7h 40m | Aer Lingus | 3×/wk |
| 3 | PIT to KEF Reykjavik, Iceland | 2,788 mi | ~6h 20m | Icelandair | 3×/wk |
| 4 | PIT to SFO San Francisco, United States | 2,248 mi | ~5h 13m | United Airlines | 2/day |
| 5 | PIT to SMF Sacramento, United States | 2,185 mi | ~5h 6m | United Airlines | weekly |
| 6 | PIT to LAX Los Angeles, United States | 2,131 mi | ~4h 59m | American Airlines, United Airlines, and Breeze | 2-3/day |
| 7 | PIT to SEA Seattle, United States | 2,120 mi | ~4h 57m | Alaska Airlines | 2/day |
| 8 | PIT to SAN San Diego, United States | 2,102 mi | ~4h 55m | Southwest Airlines and Breeze | 1/day |
| 9 | PIT to RNO Reno, United States | 2,076 mi | ~4h 52m | Sun Country Airlines | weekly |
| 10 | PIT to LAS Las Vegas, United States | 1,906 mi | ~4h 31m | Southwest Airlines | 1-2/day |
| 11 | PIT to PHX Phoenix, United States | 1,810 mi | ~4h 19m | Southwest Airlines and American Airlines | 2-3/day |
| 12 | PIT to PUJ Punta Cana, Dominican Republic | 1,671 mi | ~4h 2m | Allegiant Air | weekly |
| 13 | PIT to SLC Salt Lake City, United States | 1,655 mi | ~4h | Delta Air Lines | 1/day |
| 14 | PIT to CUN Cancun, Mexico | 1,400 mi | ~3h 28m | Allegiant Air and Southwest Airlines | weekly |
| 15 | PIT to DEN Denver, United States | 1,287 mi | ~3h 14m | Southwest Airlines and United Airlines | 4-5/day |
| 16 | PIT to AUS Austin, United States | 1,210 mi | ~3h 5m | Southwest Airlines and Allegiant Air | 1-2/day |
| 17 | PIT to HOU Houston, United States | 1,131 mi | ~2h 55m | Southwest Airlines | 1/day |
| 18 | PIT to IAH Houston, United States | 1,117 mi | ~2h 53m | United Airlines | 2-3/day |
| 19 | PIT to EYW Key West, United States | 1,105 mi | ~2h 52m | Allegiant Air | 2×/wk |
| 20 | PIT to NAS Nassau, Bahamas | 1,080 mi | ~2h 49m | Saga Airlines | weekly |
| 21 | PIT to DFW Dallas, United States | 1,066 mi | ~2h 47m | American Airlines | 4-5/day |
| 22 | PIT to DAL Dallas, United States | 1,059 mi | ~2h 46m | Southwest Airlines | 1/day |
| 23 | PIT to MIA Miami, United States | 1,015 mi | ~2h 41m | American Airlines and Southwest Airlines | 2-3/day |
| 24 | PIT to FLL Fort Lauderdale, United States | 996 mi | ~2h 38m | Southwest Airlines and JetBlue Airways | 2-3/day |
| 25 | PIT to RSW Fort Myers, United States | 968 mi | ~2h 35m | Southwest Airlines and Breeze | 1-2/day |