Her television acting credits include guest appearances on Law & Order: Special Victims Unit, Criminal Minds, The Bold and the Beautiful, and The Vampire Diaries.

Ezarik also appeared as a main character on the first and fourth seasons of the YouTube Premium murder-mystery reality series Escape the Night.

After graduating from the Pittsburgh Technical Institute in 2004, Ezarik landed several jobs in graphic design and video editing before starting her own business.

[17][18] She played a photojournalist covering a bank robbery in downtown Pittsburgh on the television series The Kill Point from Spike TV, which starred John Leguizamo and Donnie Wahlberg; it was filmed in May 2007.

She had been invited by a technology evangelist to film her Internet TV show at the mall instead of covering its debut at the Shadyside Apple store as she had originally planned.

[28] She covered the July 22, 2007, "The Kill Point" series premiere party live on her lifecast video stream.

[29] Ezarik was cited as being one of the website's most popular lifecasters in the October 2007 issues of both The New York Times and The Wall Street Journal.

Ten days after its initial posting, the video had been viewed more than 2 million times on the Internet, and received international news coverage.

[35] Ezarik was also featured in the August 28, 2007 weekly installment of Kevin Sites' People of the Web series on Yahoo!

Sites said she was "the star of this network so far," and said "she has model good looks and easy cyber savvyness that attracts both technophiles and casual users alike."

When Sites asked her to turn off her lifecasting equipment later in the interview, he noted that "at once the conversation seemed more relaxed and natural," and she discussed the difficulty of having people watching and publicly judging her all day.

[40] That June Ezarik was named by Intel and its PR firm Ogilvy & Mather to a 10-member social media strategy advisory board.

[42] When Ezarik first moved to Los Angeles, she was managed by Richard Frias who also manages YouTube celebrities HappySlip and KevJumba,[23] but according to a post on Ezarik's alternate Twitter account she was unmanaged and earned money by appearing at conferences and in online promotional spots.

[23] The series of ads, which features herself and Karen Nguyen who is a well-known blogger, has not been viewed as successful in the advertising industry.

[45] Ezarik was also hired to appear in three commercials for a national TV ad campaign for Mozy, an award-winning online backup and recovery system.

[57] She was nominated at the 4th Streamy Awards in 2014 for Best Collaboration with Rooster Teeth, Freddie Wong, Greg Miller, and Adam Kovic.

[62][63] On June 13, 2020, along with her sister Jenna, she hosted Same Brain, a podcast centering on technology, world news, and video games.

[65][66] She was also a contestant on the 7,000th episode of The Price Is Right on November 5, 2009, airing just one day after her appearance on Law & Order: Special Victims Unit.

She won prizes including a first-class trip to Acapulco, Mexico, an Apple Mac Pro computer, a Rolex watch, Viking cooking appliances, and a MIDI recording keyboard.

[67] According to her IMDb.com page, in 2009 and 2010 she earned web series guest appearance credits for BlackBoxTV Presents,[68] The Station, and Totally Sketch.

[74] After having been named "the most influential person online" in an article in Fast Company and achieving a number 6 ranking in The Daily Beast's Digital Power Index in 2012, Ezarik signed with United Talent Agency in 2013.

[78][79] On December 1, 2016, Ezarik was announced as a boardroom advisor to Arnold Schwarzenegger on the only season of The New Celebrity Apprentice.

[80] Ezarik appears as a main character on the YouTube Red murder-mystery series Escape the Night as the Gambler.

Fast Company writer David Zax described the book saying, "Ezarik wound up writing a sort of work of investigative journalism about herself by digging into a morass of tweets, photos, and videos to help remind herself who she is.

Hosted by YouTubers Justine Ezarik and her sister, Jenna, this podcast centers on technology, world news, and video games.

The pilot episode was recorded in the making of Justine's review of the Magic Keyboard for the 4th generation iPad Pro on April 20 during California's stay-at-home order due to the COVID-19 pandemic[83][84] and was later posted as a test on June 13.

[86] On April 20, while covering the pass-through charging part in her 2020 iPad Pro Magic Keyboard Review, she recorded the pilot episode under the name "Same Brain" with her sister, Jenna.