Markiplier has cried on camera in many different contexts, so the reason depends on which moment you mean. The most widely memed “crying Markiplier” clip comes from a specific video, though.
Popular meme clip
The crying image most people use as a meme comes from his reaction video to a fan-made “8 million subscribers” tribute. In that video, he breaks down because he is overwhelmed by fans’ messages about how much his content helped them and by his own wish that he could connect with each supporter personally.
He has since explained in interviews and short clips that what really made him cry was the realization that, no matter how much he cares, he can never have a truly personal connection with every single viewer who looks to him for comfort or support.
Other times he cried
Markiplier has also cried or teared up in other videos: emotional games about loss and illness, vlogs about his family and his father’s death, and other milestone fan-tribute compilations.
So if you are thinking of a different clip, it may be from one of those more personal or story-heavy videos rather than the meme image specifically.
