In the "Impossible Let's Play" series, Markiplier endures physical challenges while he plays a game. These challenges often causes him pain as he is shocked, pinched, or submerged in ice water as he plays. They are not caused by the game themselves but by objects that Mark uses while he plays, like an ice bath or hot sauce.
|"Cinnamon Challenge"||N/A||Actually was recorded in April 26, 2012 on old channel to celebrate first 1000 subscribers milestone. Markiplier just eat one spoon of cinnamon. Although there is no game, it is the original Markiplier's challenge video.||February 1, 2013|
|"TREADMILL CHALLENGE"||Surgeon Simulator 2013||Markiplier plays Surgeon Simulator 2013 while using a treadmill.||April 17, 2014|
|"HOT SAUCE CHALLENGE"||Sonic Unfair||Markiplier plays Sonic Unfair after drinking the 'Hottest Sauce In The Universe'.||April 20, 2014|
|"ELECTRIC SHOCK CHALLENGE"||Don't Let GO!||Markiplier plays with the Don't Let Go with Oculus Rift while being shocked.||April 25, 2014|
|"CLOTHESPIN CHALLENGE"||Sonic Unfair||Markiplier plays Sonic Unfair with clothespins being added to his face after each in-game death.||May 24, 2014|
|"ICE BATH CHALLENGE"||Surgeon Simulator 2013||Markiplier plays Surgeon Simulator 2013 while sitting in a bath tub full of water and ice.||June 19, 2014|
|"WAX CHALLENGE"||The Impossible Quiz Book 3||Markiplier plays The Impossible Quiz Book with his legs being waxed each time he loses.||July 8, 2014|
|"MAKEUP CHALLENGE"||The Impossible Game||Markiplier plays The Impossible Game while applying make-up to his face.||July 18, 2014|
|"WASABI CHALLENGE"||Whack Your Ex||Markiplier plays Whack Your Ex and eats small amounts of wasabi before each kill options.||September 5, 2014|
|"MUSCLE SPASM CHALLENGE!!"||Fantasia: Music Evolved||Markiplier plays Disney Fantasia Music Evolved while his arms connected to electric shock wires.||October 25, 2014|
|"Hot Sauce + I Am Bread + Sick Day CHALLENGE!!"||I am Bread||While feeling sick, Markiplier plays I Am Bread after consuming a small portion of a 5 million scoville hot sauce.||February 20, 2015|
|"PHOTOBOOTH + ICE BATH CHALLENGE"||Photo Booth||Description needed||December 12, 2015|
- The series is meant to push Mark's physical limit so that he can provide new content to his viewers.