Note that you normally cannot leave the boss room after defeating Mom you will need to have some way to teleport out before you go in and fight Mom. This will consume the item and unlock the strange door. Bring either the Polaroid or the Negative to this door.Defeating Mother for the first time will cause a strange door to appear at the beginning of Depths II in all subsequent playthroughs of the regular path.

At the end of the Antibirth path, you will fight Mother.

Navigating the Antibirth levels is tricky you may want to look at a separate guide to learn how to acquire the Knife Pieces and reach the Corpse.

This leads to an alternate set of levels, based on the Antibirth fan mod.

Defeating Hush three times will cause a new door to appear on subsequent playthroughs whenever you defeat the boss of Basement I.

Here, you will fight a powerful boss named Hush.

On subsequent playthroughs, defeating Mom’s Heart (or its replacement, It Lives!) before the timer reaches 30:00 will cause a path to the Blue Womb to open up. Defeating Mom’s Heart in Womb II ten times will unlock a new area called “?”, also referred to as the Blue Womb.Defeating Mom in Depths II for the first time will end the game and unlock the Womb.

Unlocking tainted characters is a long process, reserved for the very end of The Binding of Isaac’s unlock order.

Binding of isaac chest