Slimes spawn in the Overworld in specific "slime chunks" below layer 40, regardless of light levels. They can also spawn in swamp biomes between layers 51 and 69 (inclusive) in light levels of 7 or less, with these layers tending to be near the surface. Slimes spawn regardless of weather conditions.

Only sizes 1, 2, and 4 (NBT Size tag values 0, 1 and 3 respectively) spawn naturally. With use of /summon, slimes can potentially range from size 1 to 127 (NBT Size tag 0–126).[verify]

Like most other hostile mobs, slimes do not spawn within 24 blocks (spherical) of any player, despawn over time if no player is within 32 blocks, and despawn instantly if no player is within the despawn radius (128 blocks in Java Edition, 44 to 128 blocks in Bedrock Edition depending on simulation distance[verify]).

A slime needs roughly a 3×2.1x3 free space to spawn. The area in which the slime spawns must be clear of solid or liquid obstructions. When a slime attempts to spawn, the game checks for the space requirement of a large slime, and the size is determined later. Therefore, since large slimes are slightly taller than 2 blocks, no slimes, regardless of size, are able to spawn at all in 2-block-high areas. Also, since large slimes are slightly wider than 2 blocks, and mobs spawn at the center of a block, having any block within the 3×2.1x3 area, even as thin as a glass pane, can prevent a slime of any size from spawning.

Slime size is affected by regional difficulty: chances range from 33% for each size at the low difficulty to 16% small, 33% medium, and 50% big with higher difficulty.

Slimes can spawn on some light-emitting blocks: