| I-90 runs along it | 18 |
| I-79's northern terminus | 28 |
| Huron's neighbour | 21 |
| Huron's cousin | 18 |
| Homophone for eerie | 19 |
| Hometown of Larry Holmes | 24 |
| HOMES's E | 13 |
| HOMES word | 10 |
| HOMES unit | 10 |
| HOMES lake | 10 |
| HOMES body | 10 |
| Home to Jerry Uht Park, where the SeaWolves play baseball | 57 |
| Home port of the U.S. brig Niagara | 34 |
| Home of the reconstructed USS Niagara | 37 |
| Home of the Freeze indoor football team | 39 |
| Home of Presque Isle Downs racetrack | 36 |
| Home of Oliver Hazard Perry's flagship Niagara | 50 |
| His name means "long tail" | 36 |
| High-snowfall Eastern city | 26 |
| Great Lakes / Atlantic Ocean link | 33 |
| Great Lake with walleye | 23 |
| Great Lake name | 15 |
| Great Lake bordering Pennsylvania | 33 |
| Great Lake bordering New York | 29 |
| Great Lake between Huron and Ontario | 36 |
| Great Lake above Niagara Falls | 30 |
| Gould railroad | 14 |
| Gannon University's home | 28 |
| Gannon University location | 26 |
| Gannon University locale | 24 |
| Gannon University home | 22 |
| Gannon U. site | 14 |
| Fourth part of HOMES | 20 |
| Fort Presque Isle site | 22 |
| Fort ___, Ont. | 14 |
| Fort ___, captured by U.S. forces in 1814 | 41 |
| Fort ____, Ont. | 15 |
| Fort _____, Ontario | 19 |
| Fisk's railroad | 19 |
| First Great Lake, alphabetically | 32 |
| Feeder of Maumee Bay | 20 |
| Famous canal in the Ramones' home state | 43 |
| Famed canal | 11 |
| Enemy of the Iroquois | 21 |
| Eastern Woodlands tribe | 23 |
| Eastern tribe overcome by the Iroquois | 38 |
| Eastern Amerind | 15 |
| Early American | 14 |
| Double A baseball team in the Eastern League's Southern Division | 68 |
| Diva Mills | 10 |
| Discovery some attribute to Jolliet | 35 |
| DeWitt Clinton's waterway | 29 |
| Detroit River's terminus | 28 |
| Detroit River destination | 25 |
| De Witt Clinton's canal | 27 |
| De Witt Clinton's "ditch" | 39 |
| Cuyahoga River outlet | 21 |
| Creepy-sounding lake name? | 26 |
| Creepy-sounding lake | 20 |
| Creepy lake? | 12 |
| County west of Wyoming | 22 |
| County south of Niagara | 23 |
| County in Pennsylvania or New York | 34 |
| County in Pa. or N.Y. | 21 |
| County in New York, Ohio or Pennsylvania | 40 |
| County in both Pennsylvania and New York | 40 |
| County east of Sandusky | 23 |
| County east of Ashtabula | 24 |
| Commodore Perry's victory site | 34 |
| Clinton's Folly canal | 25 |
| Clinton's Ditch (canal) | 27 |
| Clinton's Big Ditch | 23 |
| Cleveland's waters | 22 |
| Classic railroad name | 21 |
| City where most of Perry's ships were built | 47 |
| City that's home to the U.S. Brig Niagara | 45 |
| City that sounds mysterious | 27 |
| City or canal | 13 |
| City on its own lake | 20 |
| City on a Great Lake | 20 |
| City of 100,000+ or the lake it's on | 40 |
| City NW of Johnstown | 20 |
| City near Presque Isle | 22 |
| City near Fort Presque Isle | 27 |
| City near Chautauqua Lake | 25 |
| City named for an Indian group | 30 |
| City known for lake-effect snow | 31 |
| City in the Quaker State | 24 |
| City in the minors' Eastern League | 38 |
| City between Cleveland and Buffalo | 34 |
| City between Buffalo and Cleveland | 34 |
| City across the state from Philadelphia | 39 |
| Cherokee's kin | 18 |
| Certain Iroquoian | 17 |
| Canal with a mule named Sal | 27 |
| Canal with a "low bridge" ("ev'rybody down!") | 69 |
| Canal with 36 locks | 19 |
| Canal that originally had 83 locks | 34 |
| Canal that needed Clinton's clout | 37 |
| Canal that cost $7,143,789 to build | 35 |