Isaac will appear lying down in the center of the room, crying on the floor. He shoots 12 high-velocity tears in a radial burst and will retaliate with streams of tears when hit.
At 66% of his health, a light will shine on Isaac, and he jumps from the ground. Isaac will then start shooting 4 large purple tears, which home slightly, in all directions. He will still retaliate with some tears when hit.
Triggered near 33% of Isaac's health. Isaac will grow angel wings, smile, and start floating. White beams will be randomly shot down from the sky (Similar to Crack The Sky and White Pony), Angel Babies will start spawning frequently (up to a maximum of 6), and the same homing projectiles from before will be shot in six directions at the same time. At this point, Isaac will no longer retaliate with tears when hit.
Using The Bible during or after the fight will instantly kill the player (Similar to ??? and Satan) unless they have The Wafer item, which will deal 1/2 heart damage instead.
Using items with a high fire rate (such as Technology 2) is dangerous in this fight, as Isaac will retaliate with a very large amount of tears upon being hit, unless the player have Mom's Contacts. This also applies to effects which apply damage rapidly, such as Mom's Knife.
Applying slow effects such as Little Gish or Spider Bite to Isaac will not affect the speed of his homing tears, but will slow all normal tears.
Activating Mom's Bra or triggering the special effect of Mom's Contacts will prevent Isaac from spawning enemies or attacking at all—including when damaged—for the duration of the effect.
Isaac cannot be damaged by the Crack The Sky light beams, or by his own. However, any Angelic Babies in the fight can take a small amount of damage from his light beams.
It is possible to reduce Isaac to 0 health. If Isaac is on 0 hp, the wings and light will disappear, and Isaac will resume crying on the floor. No projectiles/beams of light will be used (just like when ??? (boss) is reduced to 0 hp). However, any angels spawned from the previous phase will still survive, and will continue to attack the player.
The third form is referenced in the Wrath of the Lamb DLC's trailer, which showed Isaac sprouting wings.
From both the original game and Rebirth, in phase 1, Isaac makes the same weeping noises as the Mulligan.
When Isaac was first added in the initial release of Wrath of the Lamb, his third form only consisted of the rays of light, except with a tremendous rate of firing.
From the original game, the picture of Isaac on Isaac's Last Will is identical to that of the Mulligan, but without the bloated head.
If the player uses The Hourglass, Isaac will fire blood tears instead of the usual blue tears and purple homing tears.
From the original game, if the player is killed by the light beams in the final stage of the battle, the Last Will will display a picture of War.