
| Preliminary Round | ||||
| Connecticut | ||||
| 10/9/21 | Danersk FC | 2 : 2 | Stamford FC | |
| 10/16/21 | R | Danersk FC | 5 : 0 | Stamford FC |
| Southern New York | ||||
| 10/9/21 | Franco Swiss | 4 : 1 | Spanish American FC | |
| 10/9/21 | Glen Cove | 5 : 0 | Hempstead House | |
| New Jersey | ||||
| 10/9/21 | Carlton Hill | 5 : 1 | Palisade Park | |
| Northern New England | ||||
| 10/9/21 | West End Polish FC | 2 : 2 | Esmond Cortex | |
| 10/15/21 | Esmond Cortex | 2 : 1 | West End Polish FC | |
| Northwestern New York | ||||
| 10/9/21 | Camera Works FC | 2 : 1 | Kodak Park FC | |
| First Round | ||||
| Eastern Bracket | ||||
| Connecticut | ||||
| 10/16/21 | Bridgeport City | 3 : 1 | Ansonia | |
| 10/22/21 | Danersk FC | 2 : 3 | St. George’s | |
| Western New England | ||||
| 10/15/21 | Chicopee Rovers | 1 : 1 | Hartford FC | |
| 10/23/21 | R | Hartford FC | 1 : 0 | Chicopee Rovers |
| 10/16/21 | Manchester FC | 0 : 2 | Falco AA | |
| Eastern Pennsylvania | ||||
| 10/15/21 | M.E. Smith | 3 : 0 | Canadian War Vets | |
| 10/15/21 | Hibernains | 0 : 1 | Fleischer Yarn | |
| 10/15/21 | Philadelphia FC | 8 : 2 | Kingessing | |
| 10/15/21 | Bethlehem Steel | 4 : 0 | Ascension FC | |
| 10/22/21 | Fairhill | 3 : 0 | Disston Saw | |
| New Jersey | ||||
| 10/16/21 | Babcock & Wilcox | 4 : 3 | Sprague FC | |
| 10/16/21 | Carlton Hill | 2 : 3 (aet) | Antler FC | |
| 10/23/21 | Harrison FC | 4 : 0 | Napier FC | |
| 10/23/21 | Celtics FC | 5 : 0 | Federal FC | |
| Southern New York | ||||
| 10/16/21 | Glen Cove | 1 : 1 (aet) | Yonkers Thistle | |
| 10/23/21 | R | Glen Cove | 0 : 3 | Yonkers Thistle |
| 10/16/21 | Greenpoint | 1 : 1 | Franco Swiss | |
| 10/23/21 | R | Greenpoint | 1 : 0 | Franco Swiss |
| 10/16/21 | Todd Shipyards | 8 : 2 | Brooklyn FC | |
| 10/16/21 | Viking AC | 8 : 2 | Brooklyn Hibernian | |
| 10/16/21 | New York FC | 7 : 0 | West Harlem Catholic | |
| Northwestern New York | ||||
| 10/16/21 | Rochester City Moose | 3 : 1 | Camera Works | |
| 10/16/21 | Rochester Celtic | 2 : 1 | General Electric | |
| Northern Massachusetts | ||||
| 10/5/21 | Arlington Mills | 0 : 3 | American Woolen Co. | |
| 10/15/21 | Massachusetts Cotton Mills | 0 : 1 | Abbot Worsted | |
| 10/15/21 | Charlestown | w/o | General Electric | |
| 10/15/21 | Grey & Davis | 2 : 0 | Fore River FC | |
| 10/22/21 | Roxbury | 1 : 6 | Smith & Dove | |
| Southern New England | ||||
| 10/12/21 | Prospect Hill | 0 : 5 | Fall River FC | |
| 10/15/21 | J & P Coats | 3 : 0 | Fall River Rovers | |
| 10/15/21 | Ashton & Berkley | 3 : 1 | Clan Cameron | |
| 10/15/21 | Sayelsville | 2 : 0 | British Canadian FC | |
| 10/15/21 | St. Michael’s | 5 : 1 | Crompton | |
| 10/22/21 | Fairlawn Rovers | 3 : 0 | Westerly United | |
| 10/22/21 | Lonsdale Mills | 4 : 0 | Esmond Cotex | |
| Western Bracket | ||||
| Illinois & Wisconsin | ||||
| 10/16/21 | Gary FC | 2 : 1 | Sparta Union | |
| 10/16/21 | Thistles FC | 4 : 1 | Norwegian American FC | |
| 10/30/21 | Harvey FC | 0 : 0 | Alverno AA | |
| 11/6/21 | R | Alverno AA | 1 : 3 | Harvey FC |
| Missouri | ||||
| 10/16/21 | Johnston City | 1 : 0 | West Frankfort | |
| 10/16/21 | Prendergast | 0 : 3 | Paulian K of C | |
| 10/16/21 | Gillespie Moose | 2 : 1 | Wilsonville United | |
| Ohio | ||||
| 10/16/21 | Goodyear FC | 0 : 4 | Firestone FC | |
| 10/16/21 | Lorain Eagles | 0 : 1 | Magyar American FC | |
| 10/23/21 | Kenmore FC | 1 : 3 | White Motors | |
| Michigan | ||||
| 10/16/21 | Caledonian FC | 2 : 1 | Walkerville | |
| 10/16/21 | Ulster | 4 : 2 | Conubians | |
| 10/23/21 | Roses FC | 3 : 0 | Magyar FC | |
| 10/23/21 | Detroit FC | 1 : 2 | Scarlet Runners | |
| Western Pennsylvania | ||||
| 10/16/21 | Cuddy AC | 1 : 0 | Carnegie FC | |
| 10/16/21 | Madison FC | 0 : 3 | Moon Run | |
| 10/16/21 | Curry FC | 1 : 3 | Dunlevy | |
| Second Round | ||||
| Southern New York | ||||
| 11/5/21 | New York Field Club | 5 : 1 | Fairhill | |
| 11/5/21 | Todd Shipyards | 6 : 1 | Yonkers Thistle | |
| 11/6/21 | Viking AC | 2 : 1 | Greenpoint | |
| New Jersey | ||||
| 11/5/21 | Jersey City Celtics | 1 : 3 | Harrison SC | |
| 11/6/21 | Antler | 2 : 0 | Babcock & Wilcox | |
| Connecticut | ||||
| 11/6/21 | Bridgeport City | 1: 3 | St. George’s | |
| Western New England | ||||
| 11/5/21 | Hartford | 2 : 8 | Falco AA | |
| Eastern Pennsylvania | ||||
| 11/5/21 | Philadelphia FC | 4 : 1 | M.E. Smith | |
| 11/5/21 | Fleisher Yarn | 4 : 1 (aet) | Bethlehem Steel | |
| Northwestern New york | ||||
| 11/6/21 | Rochester Celtic | 1 : 2 | Rochester City Moose | |
| Northern Massachusetts | ||||
| 11/5/21 | Abbot Worsted | 2 : 0 | American Woolen | |
| 11/5/21 | Grey & Davis | 4 : 2 | Smith & Dove | |
| Southern New England | ||||
| 11/5/21 | Saylesville | 9 : 0 | Ashton & Berkeley | |
| 11/5/21 | Fall River FC | 6 : 0 | Lonsdale Mills | |
| 11/5/21 | Fairlawn Rovers | 2 : 0 | Charlestown | |
| 11/5/21 | St. Michaels | 0 : 2 | J & P Coats | |
| Western Bracket | ||||
| Illinois & Wisconsin | ||||
| 11/6/21 | Swedish American FC | 2 : 3 | Johnston City | |
| 11/6/21 | Thistles FC | 0 : 1 | Pullman | |
| 11/3/21 | Gary | 0 : 3 | Simmons SC | |
| 11/6/21 | Bricklayers FC | 1 : 0 | Olympia | |
| 11/20/21 | Harvey FC | 2 : 4 | Rangers | |
| Missouri | ||||
| 11/13/21 | Springfield | 0 : 1 | Paulian | |
| 11/13/21 | Gillespie | 1 : 1 | St. Leo’s | |
| 11/24/21 | R | St. Leo’s | 3 : 4 | Gillespie |
| 11/20/21 | DeAndreis | 1 : 2 | Ben Miller FC | |
| 11/20/21 | St. Louis Screw | 1 : 2 | Scullin Steel | |
| Michigan | ||||
| 11/6/21 | Industrial FC | 1 : 0 | Scarlet Runners | |
| 11/6/21 | Pontiac City | 3: 3 | Roses FC | |
| 11/13/21 | R | Roses FC | 3 : 2 | Pontiac City |
| 11/6/21 | Caledonia FC | 4 : 1 | Ulster | |
| Ohio | ||||
| 11/13/21 | Firestone FC | 1 : 2 | Magyar American FC | |
| Firestone protest upheld, replay ordered | ||||
| 11/27/21 | R | Firestone FC | 1 : 3 | Magyar American FC |
| 11/13/21 | White Motors | 4 : 2 | Cuddy | |
| Curry protest upheld, replay ordered | ||||
| 12/4/21 | R | White Motors | 0 : 0 | Cuddy |
| Match awarded to White Motors | ||||
| Third Round | ||||
| Eastern Bracket | ||||
| 11/26/21 | Fall River FC | 1 : 2 | J & P Coats | |
| 11/26/21 | Holyoke Falco | 5 : 2 | St. George’s | |
| 12/11/21 | Todd Shipyards | 5 : 3 | New York Field Club | |
| 11/26/21 | Grey & Davis | 0 : 2 | Abbot Worsted | |
| 11/24/21 | Fairlawn Rovers | 1 : 0 | Sayes Finishing Plant | |
| 12/11/21 | Harrison SC | 5 : 0 | Antler S.C. | |
| 12/18/21 | Viking FC | 4 : 3 | Moose FC | |
| 11/26/21 | Fleisher Yarn | 5 : 0 | Philadelphia Field Club | |
| Western Bracket | ||||
| 11/31/21 | Simmons FC | 4 : 2 | Bricklayers FC | |
| 12/4/21 | Pullman FC | 2 : 0 | Rangers FC | |
| 12/4/21 | Scullin Steel | 2 : 0 | Johnston City | |
| 12/4/21 | Arden | 3 : 0 | Dunlevy | |
| 12/4/21 | Industrial FC | 1 : 1 | Roses FC | |
| 12/11/21 | R | Roses FC | 1 : 2 | Industial FC |
| 12/11/21 | Ben Miller FC | 3 :1 | Paulian K of C | |
| 12/11/21 | White Automobile | 0: 0 (aet) | Magyar American FC | |
| 12/18/21 | R | White Automobile | 1 : 0 (aet) | Magyar American FC |
| 12/11/21 | Gillespie | 1 : 1 | Caledonian FC | |
| 12/18/21 | R | Caledonian FC | 6 : 0 | Gillespie |
| Fourth Round | ||||
| Eastern Bracket | ||||
| 12/24/21 | J & P Coats | 3 : 4 | Hoyloke Falco | |
| 12/25/21 | Vikings FC | 2 : 6 | Harrison S.C. | |
| 12/26/21 | Philadelphia Field Club | 1 : 4 | Todd Shipyards | |
| 12/24/21 | Fairlawn Rovers | 1 : 1 | Abbot Worsted | |
| 1/8/22 | R | Abbott Worsted | 2 : 0 | Fairlawn Rovers |
| Western Bracket | ||||
| 12/26/21 | Arden FC | 2 : 0 | White Automobile | |
| 12/25/21 | Caledonia FC | 1 : 0 | Industrial FC | |
| 12/25/21 | Pullman FC | 3 : 2 (aet) | Simco FC | |
| 12/18/21 | Scullin Steel | 3 : 0 | Ben Miller FC | |
| Quarterfinals | ||||
| 1/1/22 | Scullin Steel | 3 : 0 | Pullman FC | |
| 1/15/22 | Caledonia FC | 3 : 2 | Arden FC | |
| 2/5/22 | Abbot Worsted | 3 : 1 | Holyoke Falco | |
| 2/12/22 | Harrison SC | 0 : 1 | Todd Shipyard | |
| Semifinals | ||||
| 1/22/22 | Scullin Steel | 4 : 0 | Caledonia FC | |
| 2/25/22 | Todd Shipyards | 2 : 1 | Abbot Worsted | |
| Final | ||||
| at High School Field – St. Louis, Missouri | ||||
| 3/19/22 | Scullin Steel | 3 : 2 | Todd Shipyards | |
| KEY – w/o – Walkover, R – Replay | ||||