| Rank | City | State | Population 2020 Census |
| 1 | Chicago-Naperville-Joliet | IL | 9,618,502 |
| 2 | Detroit | MI | 4,392,041 |
| 3 | Minneapolis–St. Paul | MN | 3,690,261 |
| 4 | St. Louis | MO, IL | 2,820,253 |
| 5 | Cincinnati | OH, KY, IN | 2,256,884 |
| 6 | Kansas City | MO, KS | 2,192,035 |
| 7 | Columbus | OH | 2,138,926 |
| 8 | Indianapolis-Carmel-Anderson | IN | 2,111,040 |
| 9 | Cleveland-Elyria | OH | 2,077,240 |
| 10 | Milwaukee-Waukesha | WI | 1,574,731 |
| 11 | Grand Rapids-Kentwood | MI | 1,087,592 |
| 12 | Omaha-Council Bluffs | NE, IA | 967,604 |
| 13 | Dayton | OH | 814,049 |
| 14 | Des Moines-West Des Moines | IA | 709,466 |
| 15 | Akron | OH | 702,219 |
| 16 | Madison | WI | 680,796 |
| 17 | Wichita | KS | 647,610 |
| 18 | Toledo | OH | 646,604 |
| 19 | Lansing-East Lansing | MI | 541,297 |
| 20 | Youngstown-Warren-Boardman | OH | 541,243 |
| 21 | Springfield | MO | 475,432 |
| 22 | Fort Wayne | IN | 419,601 |
| 23 | Flint | MI | 406,211 |
| 24 | Peoria | IL | 402,391 |
| 25 | Canton-Massillion | OH | 401,574 |
| 26 | Davenport-Moline-Rock Island | IA, IL | 384,324 |
| 27 | Ann Arbor | MI | 372,258 |
| 28 | Lincoln | NE | 340,217 |
| 29 | Rockford | IL | 338,798 |
| 30 | Green Bay | WI | 328,268 |
| 31 | South Bend-Mishawaka | IN, MI | 324,501 |
| 32 | Evansville | IN | 314,049 |
| 33 | Duluth | MN, WI | 291,638 |
| 34 | Sioux Falls | SD | 276,730 |
| 35 | Cedar Rapids | IA | 276,520 |
| 36 | Kalamazoo-Portage | MI | 261,670 |
| 37 | Fargo | ND, MN | 249,843 |
| 38 | Appleton | WI | 243,147 |
| 39 | Topeka | KS | 233,152 |
| 40 | Rochester | MN | 226,329 |
| 41 | Lafayette-West Lafayette | IN | 223,716 |
| 42 | Champaign-Urbana | IL | 222,538 |
| 43 | Columbia | MO | 210,864 |
| 44 | Springfield | IL | 208,640 |
| 45 | Elkhart-Goshen | IN | 207,047 |
| 46 | St. Cloud | MN | 199,671 |
| 47 | Racine | WI | 197,727 |
| 48 | Saginaw | MI | 190,124 |
| 49 | Terre Haute | IN | 185,031 |
| 50 | Joplin | MO | 181,409 |