The Lost is unlocked by dying consecutively with certain characters, with no other deaths. Deaths must be completed in the order shown here, and seeds can be used for the runs except for the last with Azazel:
The Lost will be unlocked after dying to Satan's attack.
Multiple lives (for example, obtained by Dead Cat) must be depleted before the intended death, as deaths while having extra lives do not count as a game loss.
Having any mods installed that triggers the mod flag will make The Lost unobtainable. In order to fix this problem, all mods have to be removed.
The game cannot be won as any character required to unlock it when unlocking it.
Champion versions of monsters and bosses will count for the death criteria.
Runs can always be safely reset.
It should be noted that Mom's Foot's stomp counts as explosive damage, which makes Pyromaniac a problematic choice when trying to complete Step 3.
Picking the wrong character while unlocking him doesn't mess up the unlocking process.
Quitting and Restarting the game in the middle of the unlocking process doesn't mess it up.
Picking up Lazarus' Rags, Judas' Shadow, or Ankh should be avoided. These items will revive the current character as a different one and therefore prevent the current unlock-step from being fulfilled.
By changing a file parameter, an unsuccessful try can be undone:
Backup the file Options.ini found in the Documents\My Games\Binding of Isaac Rebirth by making a copy of it in the same folder.
Open the original file with Notepad and change the SteamCloud parameter in it to 0. This will disable Steam Cloud gamesaves synchronization.
After an unsuccessful try, delete the original file and rename the backup copy with the name of the original file: Options.ini
Repeat steps 1 after each successful run until you unlock The Lost.
When finished, open the original file and restore the SteamCloud parameter in it to 1. This will enable SteamCloud gamesaves synchronization again.
PC GPE3 2T1H (Must be on Normal difficulty. 2 Mullibooms south of starting point. Use the sacrifice room above to damage yourself first)
PC PS4 JTMD EZPF (Must be on Normal difficulty. One mulliboom directly below the starting. Go left first to get weakened)
PC GH9Y FSA8 (Hard difficulty, series of rooms containing mullibooms going down)
PC Q2V4 YZET (Hard difficulty, Cellar needs to be unlocked, 2x2 room full of mullibooms (about 6/7) when going up)
Vita GQHN NMKN (Go left, 4+ Mullibooms)
3DS 6Z2L AZ6J (Go left, 4+ Mullibooms)
PC ALFA 0NTS (Recommended Normal difficulty. Pyro in the first Treasure Room, adjacent to spawn)
PS4 FDRG 0CTE (Pyro in the first Treasure Room, adjacent to spawn)
Vita DXVW MQCF (Pyro in the first Treasure Room)
3DS YGDC T8SL (10 bombs in the first Treasure Room)
PC YR8E YXDV (Must be on Normal difficulty. Polyphemus in the first Treasure Room. Do not take devil deals, as Trinity Shield and Sacred Heart will be available in Angel Rooms. Keep the Book of Belial to ensure they show up. Also, from the pills from Mom's Coin Purse (1st boss, Duke of Flies), take the orange (Health Up) then the white one (Full Health), ignore the blue ones (Speed Down)).
PC N0G3 VLD4 (Both modes) - Dr. Fetus on floor 1, and Ipecac on floor 2.
PS4 DMTM NRD9 (Do not making a Devil Room deal in Basement II will spawn an Angel Room with Holy Grail in Caves I. Collecting everything grant huge tears.
3DS 180Y 7RDC (Lots of health early (Rosary in first Treasure room), good pickups (Mulligan is in second Treasure room, Dr Fetus and Mr Mega in the third and fourth). Skip the first Devil deal, as the Angel deals are Sacred Heart, Mitre, and Scapular. Remember to trigger scapular before entering the Mom fight if you take it, as the immediate foot stomp may leave you with the bonus soul heart.)
PC HNA6 WEK7 (Dead Cat and Holy Mantle on first floor, helpful for practice runs)