Fischbach was born at the Tripler Army Medical Center in Honolulu, Hawaii. His father Cliffton M. Fischbach, a German American, served in the U.S. Army. While stationed in Korea, he met Fischbach’s mother, a native Korean. After he was born, his family moved to Cincinnati, Ohio where he was raised. He attended Milford High School where he was a member of the school’s marching band and graduated in 2007. He has an older brother, Jason Thomas Fischbach (known as Tom Fischbach), an artist and author of the webcomic Twokinds. While Tom Fischbach is featured in some videos, he mostly stays away from allowing his face to be filmed.

Fischbach first joined YouTube on March 6, 2012, creating a channel under the username “Markiplier”, and uploaded his first video on April 4, 2012 (which is no longer on YouTube). Fischbach’s original intent for the channel was sketch comedy where he would be portraying all of the characters in the sketches. This led to the creation of the name “Markiplier”, a portmanteau of Mark and multiplier. Fischbach’s first series was a playthrough of the video game Amnesia: The Dark Descent. After playing several other game series, including Penumbra and Dead Space, YouTube banned Fischbach’s AdSense account, and he created a new channel on May 26, 2012, markiplierGAME.

In 2014, the MarkiplierGAME channel was listed on NewMediaRockstars Top 100 Channels, ranked at number 61. That year, Fischbach announced he was planning to move to Los Angeles, California to be closer to other resources for his channel, such as the YouTube Space and other content creators. Fischbach and fellow YouTuber Jenna Mae appeared on Jimmy Kimmel Live! in September 2015 following backlash Kimmel received regarding jokes he made about YouTube and Let’s Play videos. In 2015, he was rated sixth in a list of the twenty most influential celebrities among teenagers in the United States.

Fischbach joined the board of comic book publisher Red Giant Entertainment in November 2014. In June of that year at the San Diego Comic-Con, he co-hosted a panel with figures from the company including CEO Benny R. Powell, and writers David Campiti, Mort Castle, David Lawrence, and Brian Augustyn. In 2016, it was announced that he would appear in his own line of comics.

Beginning in 2015, Fischbach lived with fellow YouTubers Daniel Kyre and Ryan Magee, who created and ran the YouTube sketch comedy and music channel Cyndago. Matt Watson from Kids w/ Problems later joined Cyndago after they moved to Los Angeles. Their work was noted for having unexpected endings and dark, often disturbing, humor. Cyndago disbanded following the death of Daniel Kyre. At the time of their disbandment, the group made forty sketches and fourteen original songs, many of them featuring Fischbach. After the death of Daniel Kyre and disbandment of Cyndago, Fischbach temporarily went on hiatus from September 17, 2015 to October 5, 2015. He returned and reached 10 million subscribers on October 15, 2015.

In January 2016, Fischbach signed to Revelmode, a subnetwork to Maker Studios, along with other YouTubers such as Jacksepticeye and PewDiePie. Revelmode was disbanded in early 2017 as a result of PewDiePie being cut from Maker Studios. He subsequently signed to another Maker Studios sub-network, Polaris.

Throughout 2016, Fischbach moved some of his focus to comedy sketches, showing his aspiration of improvisational theatre. In 2017, Fischbach posted an interactive Choose Your Own Adventure-style video titled “A Date With Markiplier”, which was well-received by fans.

Fischbach signed with Endeavor in late 2016, having expressed interest in branching out from YouTube content.

Since 2017, he has voiced the character 5.0.5 in the Cartoon Network series Villainous.

Fischbach has participated in multiple charity live streams and fundraisers. In 2017, Forbes reported that Fischbach and his fans raised around $3 million for charity through these events. In March 2018, in celebration of reaching 20 millions subscribers, Fischbach announced he would donate all proceeds from a 48-hour sale of his “Tasteful Nudes” Charity Calendar to the Cancer Research Institute; he raised over $490,000 for the charity.

On March 29, 2018, Fischbach announced his YouTube channel had surpassed 20 million subscribers.

On June 19, 2018, Fischbach’s step-niece, Miranda, was killed in a car accident at the age of 19. He released a video 5 days later on June 24 titled “update” announcing the news and that he would not be able to make videos for a while. Two days later on June 26, Fischbach released a video titled “Special Message from Miranda’s Dad”, where Mark talked more about Miranda and Miranda’s dad, Michael, thanking Fischbach’s fanbase.

In 2018, Markiplier announced the launch of a new fashion brand called Cloak, in a joint venture with Jacksepticeye. In 2020, fellow YouTuber and streamer Pokimane joined Cloak as a partner and creative director.

In October 2019, Fischbach announced a new Choose Your Own Adventure story similar to 2017’s A Date With Markiplier, a YouTube Originals production titled A Heist With Markiplier. Produced by Fischbach and Rooster Teeth, this series contains 31 possible endings and stars other YouTubers such as Rosanna Pansino, Matthew Patrick, and Game Grumps.

On November 15, 2019, Fischbach launched a new channel with fellow YouTuber Ethan Nestor called Unus Annus, a channel which planned to upload a video every day for one year, after which the channel would be deleted along with its videos. The channel rose to early success, gaining 1 million subscribers in its first 5 days and over 11.5 million video views in its first week. Following a commemorative live stream that peaked at over 1.5 million concurrent viewers, the channel was deleted on November 14, 2020 at 12:00 a.m PST.