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Not to be confused with "play as ??? and beat Isaac (Cathedral boss)", which unlocks the D6.
Now that this is clear, if it doesn't answer your question, a few of mine:
- How do you check if it's locked? Never refer to the item list, it shows items you picked up during runs, not unlocked ones. The secrets menu is the only 100% way to know if something is unlocked or not. The D20 is secret number 49.
- If it is locked, how do you play your runs? You can't unlock anything during challenges, daily challenges, seeds, or victory laps (the thing that start when you kill the Lamb and say "yes").
okay, I said something stupid because it's unlocked. Maybe I'm remembering wrong, but didn't Isaac start with the D20 once he unlocked it?
like the previous guy said, defeat blue baby as isaac