Mom is the boss found in the second level of Chapter 3 (The Depths and Necropolis) and is the final boss for the game's prologue. The mother of Isaac, she is a delusional woman who believes that the hallucination she hears telling her to murder her son is the voice of God. If Isaac is going to escape from the terror under the house, he's going to have to kill her.
Mom's Foot: Mom's main attack, used when Isaac is not near any of the four doors. Deals damage in a radius approximately equivalent to the shadow that it casts before contacting. This attack can damage other enemies in the room and even Mom herself, if the foot lands on Flesh or an Eye.
Mom's Hand: An alternate attack used when Isaac is too close to a door between stomps. Mom will stop stomping for a short period if this attack is used. However, this attack happens very quickly and is much harder to dodge than the foot.
Mom's Eye: Periodically appears in one of the four doorways. The eye does not attack or spawn enemies, offering a short period of time in which to damage Mom. (Note: Mom's red champion version (see below) will fire a triple blood shot from the eye)
Mom's Flesh: A lump of flesh that will appear and summon an enemy next to it. Mom can have up to 4 additional enemies assisting her during the fight.
Mom, like other bosses, has a single health bar that depletes when any of her body parts are damaged. All enemies and body parts will be destroyed when her health is brought to zero. A common and effective strategy is to stay in the center area of the room. This will prevent Mom's hand from attacking and causing damage before it can be dodged. Use Mom's friendly fire stomp damage to help keep the spawned enemies at bay during the fight; you might have to deal with range attacking enemies which won't follow you to the center of the room. The corners of the room also do not cause the hand to attack, but may contain rocks that obstruct Isaac's path and might allow pursuing enemies to catch up. Use bombs or Mom's foot to clear a path of evasion against the enemies and foot damage.
As with all bosses, having Mom's Bra is just as effective against Mom as it is against any other boss. Use the time that she's frozen to deal as much damage to the leg as possible.
You can also stand near her eyes/other parts when she's about to stomp. If you get away at the last second, she'll stomp on her self, dealing massive damage to her.
Mom will not use her stomp attack if Isaac is standing very close to any of the 4 doors. (This seems to be implemented so that players cannot force mom to stomp herself without at least risking to take damage). So you just can stand there, shoot at the door and dodge spawned enemies until you kill her, scoring yourself a very easy victory.
The Bible is Mom's major weakness and can be used to defeat the whole encounter instantly. This holds true also for Mom's Heart and It Lives.
NOTE:The Bible should not be confused with the similar looking Book Of Revelations item which will not instant-kill her. The Bible is brown with a black cross, while the Book of Revelations is purple with a white cross.
Unlike lesser bosses, killing Mom ends the battle immediately, destroying all remaining enemies. (A Gaper can survive in the form of a Pacer or a Gusher. A Globin is also able to survive as a puddle that will regenerate shortly after. The Chest /Trapdoor will still appear after the Monster's death.)
After defeating Mom, teleporting is the only way to exit the room, as the doors are destroyed when Mom is killed. Make sure to check every room and pick up every item on the floor before beginning the encounter (A door to the Devil Room may appear after a teleportation.)
If Isaac is standing in the shadow animation of Mom's stomping attack when she is killed, the player will still receive 1 Heart of damage. It is unavoidable.
Mom's visuals came from the character in Edmund's unreleased children's book Mom's Hungry.
Since the Bible is Mom's greatest weakness, it's completely ironic that Mom is knocked out senseless after getting hit by said book during the game's first ending.
While in the Mom fight, Mom's eye will show every time she says Isaac's name. However, that is not true in Rebirth.
Sometimes killing Mom will trigger the sound of a devil/angel room opening, but no room will actually open. If you teleport out of the boss room and re-enter, the devil/angel room will show itself.
If you've just killed Mom for the first time, or are playing a particular Wrath of the Lamb Challenge, teleporting while Mom's death animation is playing (before the cutscene) will make you stuck inside of the level, because the next level door never would appear in the first place. The only way out is teleporting to the I AM ERROR room or using We Need To Go Deeper!. Oddly enough, it can make the Devil Room appear.
If you are in the Depths XL or Necropolis XL, then the boss right before Mom will also play her music, but Mom will still play her own music. This also occurs with Mom's Heart/It Lives! in Womb XL and Utero XL.
Using The Candle in the direction of the doors while nothing is showing will drain Mom's health.
Edmund confirmed that the Polaroid always dropping is a bug. This, however, can not be fixed since the game isn't able to receive any further updates.
After killing Mom the player will sometimes take damage, despite not being hit by anything.
As of version 1.4, Mom will always drop The Polaroid (provided you've unlocked it). This was confirmed to be a bug.