19 cities
| City | Rank | 2025 Pop. ↓ | 2020 Pop. | Annual Change | Density | Area (mi²) | Type |
|---|---|---|---|---|---|---|---|
| Cape Girardeau | 1 | 41,076 | 39,786 | 0.63% | 1,404 | 29 | City |
| Jackson | 2 | 16,048 | 15,453 | 0.75% | 1,493 | 11 | City |
| Jackson | 3 | 1,216 | 1,145 | 0.5% | 13 | 97 | Township |
| Jackson | 4 | 1,187 | 1,148 | -0.25% | 16 | 76 | Township |
| Jackson | 5 | 912 | 985 | -1.83% | 12 | 75 | Township |
| Jackson | 6 | 710 | 702 | 0% | 15 | 49 | Township |
| Gordonville | 7 | 631 | 621 | 0.32% | 809 | 1 | Village |
| Jackson | 8 | 553 | 539 | 0.73% | 8 | 70 | Township |
| Delta | 9 | 380 | 375 | 0.26% | 964 | 0 | City |
| Altenburg | 10 | 335 | 342 | -0.59% | 319 | 1 | City |
| Oak Ridge | 11 | 238 | 235 | 0% | 403 | 1 | Town |
| Jackson | 12 | 191 | 189 | 0.53% | 3 | 56 | Township |
| Haywood City | 13 | 135 | 133 | 0% | 315 | 0 | Village |
| Jackson | 14 | 131 | 138 | -2.24% | 3 | 41 | Township |
| Jackson | 15 | 127 | 126 | 0% | 4 | 30 | Township |
| Pocahontas | 16 | 97 | 94 | 0% | 942 | 0 | Town |
| Allenville | 17 | 95 | 94 | 0% | 613 | 0 | Village |
| Whitewater | 18 | 85 | 84 | 0% | 397 | 0 | Town |
| Old Appleton | 19 | 75 | 74 | 0% | 620 | 0 | Town |
Cape Girardeau is the largest city in Cape Girardeau County, with a population of 41,076.
Old Appleton is the smallest city in Cape Girardeau County, with a population of 75.
There are 19 cities in Cape Girardeau County, Missouri.