According to Deen, performing in pornographic films was his ambition since he was in kindergarten. After entering the pornography industry in 2004, he initially worked with older female performers. In 2009, he was named the "Male Performer of the Year" by AVN at the age of 22, making him the youngest actor to have won this award. Deen has a fan-following among teenage girls, a demographic that is typically not associated with the pornographic industry. In February 2012, ABC Nightline aired the feature Porn's Boy Next Door, which included interviews with both Deen and his fans. One fan described him as "the Ryan Gosling of porn".
From 2005 to 2011, Deen dated fellow pornography star Joanna Angel. In an interview with The Huffington Post from July 2013, porn Actress Stoya stated that she was dating Deen. They dated from 2012 to 2014.
Deen was featured in a July 2012 GQ multi-page article, chronicling his work and personal life. GQ interviewed Deen again for an article about his workout regimen, in which he credited healthy eating habits, a "Jew stomach" and lots of sex. In 2013, Deen was listed as the only male performer to make the CNBC Dirty Dozen list of the porn industry's popular stars.
Deen has a sizable fan base; his fans, dubbed "Deenagers", have created social media fan pages on Tumblr, Pinterest and standalone fan sites. Deenagers regularly share and comment on Deen's work. In February 2013, Deen launched JamesDeenStore.com. In addition to Deen's films and adult novelties, the store features Deen's Baby Panda brand of clothing.
In June 25, 2014, Deen participated in a Reddit A.M.A.. Deen received over four thousand questions over the course of an hour, making Deen's AMA listed by Reddit as the most popular on the site as of the following morning. Questions ranged from those about his career, personal life, condom legislation, the Teen Mom Farrah Abraham sex tape and more.
In late 2015, articles in The Daily Beast and The Huffington Post referred to Deen as the "Bill Cosby of porn". Deen later gave an interview to The Daily Beast where he claimed to be "baffled" by the accusations and denied or offered counter-explanations for them.
In July 2017 Director Maria Demopoulos filed a lawsuit against Deen for blocking the distribution of a documentary that addresses the numerous rape and sexual assault allegations against Deen by stealing legal releases from her office.