A desk mat won't cause uneven wear on your mousepad.

No, not really. Unless your desk mat has a weird rough texture or your mousepad is paper-thin, the desk mat acts as a neutral base. The wear on a mousepad comes from your mouse feet, your wrist, and time — not the surface underneath it.

Most mousepads are made with a cloth or hard top layer that slides fine on a desk mat. If anything, the desk mat adds cushion and prevents the mousepad from sliding around, which can actually reduce uneven wear from creasing or bunching. The only way I can imagine desk mat causing uneven wear is if the mat has raised edges or a textured pattern that creates high spots under the mousepad after months of pressure. But that’s rare with decently flat mats.

If you’re worried, rotate your mousepad 180 degrees every few months. But honestly, you won’t notice any difference.

The bigger issue is dust and crumbs getting trapped between the two — clean both occasionally and you’re fine.