| 1. |  OfficialNerdCubed | 893,392 | Nerd³ Plays... The Binding of Isaac | 20:04 |
| 2. | Millbeeful | 266,021 | The Binding Of Isaac | SHAKE OFF THE RUST - Millbee's Playthrough Part 46 | 19:04 |
| 3. | MrAndersonLP | 54,998 | Let's Play The Binding of Isaac: New Save File (Gameplay/Walkthrough) [Part 5] | 33:19 |
| 4. | Eurogamer | 28,198 | Let's Play The Binding of Isaac - Late to the Party | 48:55 |
| 5. | Dan Does | 19,294 | How to Make Lots of The Binding of Isaac Sculpts! | 5:57 |
| 6. | Storpey | 8,781 | Steve plays The Binding of Isaac (Storpey's Steam Stuff) | 23:09 |
| 7. | Chawesy | 4,788 | THE CAT MURDERED MY MOM | Cat Evolution : Alpaca Zombie! | Gameplay, Reaction | 9:00 |
| 8. | ParkyGames | 3,697 | Parky's Shorts - Wrath of The Lamb - Part 1 - Let's Do This! | 13:20 |
| 9. | MrGreenYeti | 3,459 | Let's Play The Binding of Isaac - 25 - 'Scrapping' | 28:22 |
| 10. | Evanz111 | 2,249 | The Random Commentaries: Binding of Isaac | 8:30 |
| 11. | Steejo | 2,014 | 100%ing The Binding of Isaac With Steejo Episode 83 | 9:05 |
| 12. | PyroJoe | 1,735 | PyroJoe Plays: The Binding Of Isaac! #2 | 23:09 |
| 13. | TrU3Ta1ent | 1,353 | Let's play The Binding of Isaac with hilarious commentary [part 1] FIRST RUN! | 1:30:44 |
| 14. | Marly Games | 1,274 | Let's Play A Wizards Lizard | Episode 18 [My Best Run] | 40:32 |
| 15. | PieDragonPS | 884 | The Binding of Isaac [Glitch] - 9 Lives = Lots of Boss Items | 3:36 |
| 16. | Jaru | 876 | I HATE MONSTRO!:The Binding of Isaac Let's Play w/Jaru Part 2 | 11:07 |
| 17. | Masterath Gaming | 795 | Let's Play The Binding of Isaac part 47/47: Chained no More... | 14:16 |
| 18. | RobinLSL | 766 | Let's Play The Binding of Isaac - 1 - Discovery | 51:32 |
| 19. | FlareBlitzed | 673 | Walking on a Star Unknown (RPG Maker) - Part 8 | Flare Let's Play | Yurika's Freedom | 1:00:25 |
| 20. | JustRed | 600 | The Binding of Isaac | Wrath of the Lamb Playthrough | 33:55 |
| 21. | TheXploder | 475 | Let's Play, Binding Of Isaac: Wrath of the Lamb Part 12: One Eyed Lovin | 33:29 |
| 22. | Sector Alpha Gaming | 326 | The Binding of Isaac - #2 'Let's Kill Mom Mission!' | 27:44 |
| 23. | Elanip | 317 | The Binding of Isaac: Lets Play Episode. 3 - Big Worm Had Me For Lunch | 13:39 |
| 24. | Armerus | 261 | The Binding of Isaac - GamerArmerus Playthrough/Commentry - Episode w/e | 40:05 |
| 25. | Green Man Gaming | 176 | Green Team Presents | Binding of Isaac | 5:29 |
| 26. | AlpaxLP | 175 | Channel Update 1 - Isaac, CK2, New LP | 2:51 |
| 27. | Dommy1218 | 168 | Dommy1218 plays - WHY THE F*CK IS THERE SO MUCH LOADING!? | 20:01 |
| 28. | Atomic Brainbag | 149 | BINDING OF ISAAC - Funny Poop! | 16:23 |
| 29. | MizuhoChan | 121 | Let's Play The Binding Of Isaac - Part 8 - Die Mom, Die! | 36:09 |
| 30. | Mikehyphenplays | 112 | Back down the cellar: The Binding of Issac #17 | 16:36 |
| 31. | YetiHype | 96 | Lets play The Binding of Isaac - Episode 14 - Redo | 34:38 |
| 32. | FBDC | 75 | FBDC Plays - The Binding of Isaac | 30:23 |
| 33. | falpatrick | 72 | DISAPPOINTMENT - Binding of Isaac Playthrough Part 2 | 11:24 |
| 34. | The CaffCast | 51 | CaffCast Plays - The Binding Of Isaac - Wrath Of The Lamb | 11:17 |
| 35. | JoshFTL | 44 | Binding of Isaac head2head with Eclipse the Gamer! | 30:38 |
| 36. | TophuNugget | 43 | i'm a greedy rat | 54:10 |
| 37. | Mr. Nutt | 43 | Let's Play: The Binding of Isaac | 21:29 |
| 38. | WhiteNinjaArt | 40 | The binding of isaac part3 continued full play through | 37:22 |
| 39. | AtomTheCat | 32 | Atom plays the binding of Isaac p3 (Hello darkness my good pal) | 12:45 |
| 40. | MrUnderdoglx | 32 | The Binding of Isaac Lets Play | 9:30 |
| 41. | Goth_Jester22 | 31 | The Binding Of Isaac Playthrough With Judas | 59:03 |
| 42. | Kino_Plays | 29 | Kino-Plays: The Binding of Isaac - 13/10/21 - 2 | 1:02:32 |
| 43. | StupidlyEPIC | 27 | Prime Plays The Binding of Isaac - Episode 7 | 51:54 |
| 44. | Makenshi | 16 | Let's Play: Bind of Issac E1 - Failure is considered an option | 23:18 |
| 45. | ackieforest | 15 | Let's Play The Binding of Isaac part 666 "Isaac starts a gang!" | 30:39 |
| 46. | Nick Ball | 8 | Nick Ball Plays - Binding Of Isaac - Episode 1 | 7:48 |
| 47. | CNPGames | 7 | CNPGames Plays - Binding Of Isaac - Episode 14 - Im back! | 12:25 |
| 48. | JDTSlash | 6 | Let's play: The binding of Isaac - Episode 1 (So close yet so far) | 1:46:27 |
| 49. | Tomzilla | 4 | Quick Feature - Let it die Part FINAL | 27:24 |
| 50. | Jimbo Spike | 3 | The Binding Of Isaac - Lotsa Bombs (Loud!) | 2:43 |
| 51. | IdioticUlt1mara | 2 | Idiotically Reviewing Fallen Angel | 4:01 |
