The 23 missions in Destruction of All Humans! take place in six hub levels. The player has a limited area to traverse through at first but when a mission is completed, the player is granted access to more of the level.
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While in a mission, the player is only allowed to stay in their area. If a player elects to free roam instead of taking on a mission, they can access every part of that map.
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| Mission Number | Mission Name | Mission Location |
| 1 | Destination Earth | Turnipseed Farm |
| 2 | Earth Women Are Delicious | Rockwell |
| 3 | Citizen Crypto | Rockwell |
| 4 | Alien Pool Party | Santa Modesta |
| 5 | Television of Doom | Santa Modesta |
| 6 | Aliens Stole My Brain Stem | Santa Modesta |
| 7 | This Island Suburbia | Santa Modesta |
| 8 | Teenage Zombies from Outer Space | Rockwell |
| 9 | South by Southwest | Santa Modesta |
| 10 | Foreign Correspondent | Santa Modesta |
| 11 | Suburb of the Damned | Santa Modesta |
| 12 | Whatever Happened to Crypto-136 | Area 42 |
| 13 | The Mutant Menace | Area 42 |
| 14 | The Wrong Stuff | Area 42 |
| 15 | Duck and Cover | Area 42 |
| 16 | It’s A Wonderful Armageddon | Santa Modesta |
| 17 | Furon Down | Union Town |
| 18 | Mr Crypto Goes to Capitol City | Capitol City |
| 19 | Armquist vs the Furons | Union Town |
| 20 | The Lone Gunman | Capitol City |
| 21 | The Furon Filibuster | Capitol City |
| 22 | Shocking Developments | Capitol City |
| 23 | Attack of the 50-Foot President | Capitol City |
If you like games with a sci-fi alien twist, you should check out the Aliens Fireteam Elite page on Pro Game Guides!