Isaac's Mom is the boss found in The Depths level 2 and is the final boss for the game's prologue from both The Binding of Isaac and the Rebirth remake. She is a delusional woman who hears God's voice from above telling her to sacrifice her son. If Isaac is going to escape from the terror under the house, he's going to have to kill her.
In the Wrath of the Lamb DLC, she also appears as the final boss of the alternate chapter Necropolis.
From the opening intro, Isaac's mother is a heavy-set woman with curly blond hair and wears a purple skirt with polk-a-dots.
During the boss battle, her stomping leg wears a red high-heels, and her hands with red-polished fingernails. Her eye colors are red-brown.
Behavior
She has 4 basic parts:
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.
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.
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.
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; Isaac might have to deal with range attacking enemies which won't follow him 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.
Isaac can also stand near her eyes/other parts when she's about to stomp. If Isaac 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 Isaac can only stand there, shoot at the door and dodge spawned enemies until you kill her, scoring yourself a very easy victory.
The Bible
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.
Notes
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.)
In Rebirth, if you get to Mom and kill her under 20 minutes a hole in the wall will appear, as well as a door to the Devil or even Angel Room. The hole in the wall leads to the Throwback Boss Rush Room.
Since Wrath of the Lamb, 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.
As of version 1.4, Mom will always drop The Polaroid (provided Isaac have unlocked it).
From the starting screen of the original game, her name has an exclamation point at the end. In Rebirth, unlike most other bosses, her name texture is completely red with a heart shape instead of the exclamation point.
Since that the Bible is Mom's huge weakness, it was completely ironic where Mom's being knocked out senseless after getting hit by the Bible during the game's first ending.
In Rebirth, she seems to have a new voice actor. This makes her sound less like a monster and more like a genuine person.
While she doesn't have a skirt at the top of her leg from the original game, she possess one in Rebirth.
While in the Mom fight, Mom's eye will show everytime she says Isaac's name
However, that is not true in Rebirth.
Bugs
Sometimes killing Mom will trigger the sound of a devil/angel room opening, but no room will actually open. If Isaac teleport out of the boss room and re-enter, the devil/angel room will show itself.
If Isaac has just killed Mom for the first time, or is playing a particular Wrath of the Lamb challenge, teleporting while Mom's death animation is playing (before the cutscene) will make Isaac 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 Isaac's 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.
Isaac's Mom is the boss found in The Depths level 2 and is the final boss for the game's prologue from both The Binding of Isaac and the Rebirth remake. She is a delusional woman who hears God's voice from above telling her to sacrifice her son. If Isaac is going to escape from the terror under the house, he's going to have to kill her.
"I Killed Mom!" - Defeat Mom in The Depths 2.
"The Halo" - Kill Mom or Mom's Heart using The Bible.
"Samson" - Defeat Mom by skipping out on two Treasure Rooms beforehand.
The Duke of Flies • 
Gemini • 
Monstro • 
Larry Jr. • 
Fistula • 
Gurdy • 
Peep • 
Chub • 
Loki • 
Scolex • 
Blastocyst • 
The Fallen
Monstro II
Steven • 
C.H.A.D. • 
Gish
Famine • 
Pestilence • 
War • 
Death • 
Headless Horseman
Mom • 
Mom's Heart • 
It Lives • 
Satan
