In anime, Mercer voices Levi Ackerman in Attack on Titan, Kiritsugu Emiya in Fate/Zero, Jotaro Kujo in JoJo's Bizarre Adventure, Tony Stark / Iron Man in Iron Man: Rise of Technovore and Avengers Confidential: Black Widow and Punisher, Aikurō Mikisugi in Kill la Kill, Kanji Tatsumi during the second half of Persona 4: The Animation, the second voice of Yamato in Naruto, Trafalgar Law in the Funimation dub of One Piece, Hit in Dragon Ball Super, Seijirou Kikuoka in Sword Art Online, Falco in Cyberpunk: Edgerunners, and Leorio in Hunter x Hunter.

In video games, Mercer has voiced Leon S. Kennedy in Resident Evil 6, Ganondorf in The Legend of Zelda: Tears of the Kingdom, Kurtis Stryker in Mortal Kombat 9, Chrom and Ryoma in Fire Emblem, Jack Cooper in Titanfall 2, Espio the Chameleon in Sonic the Hedgehog, Deadshot in Injustice 2, Cole Cassidy (formerly Jesse McCree) in Overwatch, Yusuke Kitagawa in Persona 5, MacCready in Fallout 4, Midas and Syd in Fortnite: Battle Royale and Fortnite: Save the World respectively, Edér Teylecg and Aloth Corfiser in Pillars of Eternity, Ex in Puyo Puyo Tetris, Gangplank and Kindred's Wolf in League of Legends, Walter in Shin Megami Tensei IV, Ira in Kingdom Hearts, Goro Majima in Yakuza: Like a Dragon, Vincent Valentine from Final Fantasy VII Rebirth, Albert Genette in Ace Combat 5 and Vecna in Dead by Daylight.

In his early career he worked as a QA tester and later associate producer on a number of Edutainment titles developed by Sound Source Interactive and TDK Mediactive.

[7][8] Mercer began his voice acting career performing English walla and additional characters in several Japanese anime, and has since also worked in cartoons, video games, and radio commercials.

He also acted in several shows from the Geek & Sundry and Nerdist networks and produced the web series Fear News with the Last Girl for FEARnet which was a 2010 Webby Awards Honoree for the Experimental & Weird category.

[17] Luke Winkie, in a human-interest story for Slate, called Mercer "an expert improviser" and "a maestro with the dice in his hands, weaving interlocking plot lines and complex thematic threads out of thin air" with "the innate ability to make a Dungeons & Dragons campaign feel like a tightly wound limited drama".

As a career voice actor, he possesses all of the subtle performance intangibles that saturate his storytelling with life: the timing, the verve, the language flourishes".

[23] In November 2019, Amazon Prime Video announced that they had acquired the streaming rights to this animated series, now titled The Legend of Vox Machina;[24][25] Mercer reprised his role as Sylas Briarwood and other characters.

[37] On March 15, 2022, a new adventure module titled Critical Role: Call of the Netherdeep (2022), with Mercer, James Haeck and Chris Perkins as lead designers, was released.

[41] The video of his proposal became popular among fans as it involved an entire escape room game he secretly created with the Critical Role cast as a surprise for Ray.