[13] DeFranco lived in a car until moving back with his father in Tampa, Florida, on condition that he would return to college, which he ultimately did not do.

[15] On September 15, 2006,[16] DeFranco created his YouTube account during his finals at East Carolina University, originally registered as "sxephil", in which he talks about "newsie type stuff, and things that matter to [him] today.

Before the YouTube partner program was available, he asked for donations from his viewers after claiming to have run out of money, and selling everything except his Mac, camera, and clothes, and overdrawing his bank account so he could spend a night in a hotel as he found it too scary sleeping in a car in Brooklyn.

[24] DeFranco used his large audience to win the Spore Creature Creator, a game promotion competition, and in doing so beat celebrities such as Stan Lee, Katy Perry, and Elijah Wood.

[10] DeFranco's large online audience also enabled him to win Wired's Sexiest Geek of 2008 competition, a reader-voted contest.

[27] In October 2008, DeFranco co-starred with Jessica Rose and Kevin Wu in Hooking Up, written and directed by Woody Tondorf as a promo for HBOLabs (the online arm of HBO).

Hooking Up is a scripted 10-episode web series set at a fictional university where the students spend most of their time emailing and using Facebook, but still manage to miscommunicate.

"[33] In 2008, he stated in an interview that his listed salary of $250,000 from a number of sources on the Internet, including and beyond YouTube, was initially a joke, but would become accurate.

[37] DeFranco's early attempts at launching channels with scopes outside of his eponymous news series included BamBamKaboosh and TheDeFrancoUpdate.

[40] Early in his YouTube career, Penna aided DeFranco, securing him coverage in news articles and magazines, such as Fast Company.

[44] Also in the month, DeFranco co-created CuteWinFail, along with Toby Turner; the online series was described by Fruzsina Eördögh of ReadWrite as "essentially the YouTube equivalent of America's Funniest Home Videos.

[59] In January 2013, DeFranco took part in a Google+ Hangout with United States Vice President Joe Biden and Guy Kawasaki, discussing gun laws.

[69] Additionally, DeFranco has organized live shows and meetup events in locations such as Arizona, Los Angeles, and Toronto.

[70][71][72] DeFranco aspired to have launched channels within his network by the end of 2013, though due to "the logistical complications of joining Discovery, adding staff and strategizing the future," those plans did not materialize.

[73] These plans once again fell through, but in 2015, DeFranco was involved in the launching of Super Panic Frenzy, a gaming network, including a YouTube channel and a Twitch live-stream show.

[77] By the end of the year, The Outline noted that DeFranco had over 13,000 Patreon subscribers donating an amount of money that while undisclosed was enough to rank him within the platform's top 20 creators.

[79] DeFranco's coverage of issues concerning YouTube culture—such as PewDiePie's alleged anti-Semitism controversy and the DaddyOFive child abuse story—were among those most cited by online and mainstream media publications.

[81][83] DeFranco's coverage and criticism of the channel sparked a community backlash and heightened media attention that led to the Martins losing custody of two of their children,[81] and ultimately being charged with and found guilty of child neglect.

[82][87] Due to hot-button topics that can arise when delivering the news, DeFranco's content is particularly prone to being deemed "unfriendly" to advertisers.

[90] In October 2018, BetterHelp gained attention from YouTube personalities after concerns were raised about alleged use of unfair pricing, paid reviews from actors, and questionable terms of service.

Both DeFranco and BetterHelp CEO Alon Matas addressed the issue, giving statements to Polygon's Julia Alexander.

[93] DeFranco launched Beautiful Bastard in February 2019, a line of hair care named after his catchphrase from the introductions of his news show.

[96] In addition to the website and YouTube channel, the Rogue Rocket network also comprised a podcast named A Conversation With, in which DeFranco hosts and interviews a subject.

[101] Sarah Kessler of Fast Company has referred to DeFranco as his generation's "Jon Stewart, if not Rupert Murdoch and News Corp".

Alex Iansiti of Huffington Post (now HuffPost) noted, "The Philip DeFranco Show is a great example of a media company to sprout out of YouTube".

[116] Dating as far back as 2008, DeFranco has been frequently cited as pondering a potential end to his eponymous news series or an exit from the platform altogether.