Millikin's art often includes self-portraits as well as portraits of celebrities and political figures. Millikin's artwork is often characterized by brilliantly colored paint brushed and smeared into expressionist swirls and spirals. His work often incorporates mixed media and found objects, such as packages of candy and spiders. His large-scale artwork takes full advantage of the internet's formal possibilities, and has incorporated animation and winding "infinite canvas" designs, going beyond the limited sizes and shapes of conventional printed pages. Millikin's works range from those made almost completely of calligraphy, typography or text (for example "My Little Brother," a first-person tale from the perspective of one conjoined twin in a love triangle) to those that are optical illusions completely abstract. Millikin's works often include text written in free verse, anagrams, ambigrams and cut-up technique poetry. Millikin's artwork has also been published in books, serialized in newspapers, and displayed in art museums.
Millikin often collaborates with artist Casey Sorrow. Together, Millikin and Sorrow created and popularized the international animal rights holiday World Monkey Day.
Millikin began drawing horror comics by age one-and-a-half, when he made crayon drawings of ghosts terrorizing him during toilet-training. By second grade, he was making teachers profane birthday cards showing his school burning down. As a youth, he was influenced by 1980s X-Men and Far Side comics and the video game Gorf. Millikin began posting comics and art on the internet using CompuServe in the 1980s, and began publishing on the World Wide Web as early as the fall of 1995.
Millikin attended art school at Michigan State University in their Honors College. He paid his way through school by working in MSU's human anatomy lab as an embalmer and dissectionist of human cadavers. While at art school, Millikin was homeless and lived in a Buick LeSabre.
In 2002, Millikin was an editor (along with Tom Hart) and contributing artist of the online alternative comics anthology Serializer. Serializer's other contributing artists also included Renée French, James Kochalka, Chris Onstad, Ryan North, Jen Sorensen, Matt Bors, Joey Comeau and Emily Horne. In 2005, Millikin was one of the artists in the Clickwheel collective that published graphic novels on the video iPod. Millikin has also been published by the webcomics sites Modern Tales and Webcomics Nation. His comics were one of the all-time most popular on Webcomics Nation. Millikin is one of the few, and first, webcomic creators successful enough to make a living as an artist.
Major recurring themes of Eric Millikin's art are portrait paintings, the supernatural, and optical illusions. He often creates self-portraits showing him falling prey to tragic death or engaging in star-crossed love affairs. For example, he is depicted engaged in activities such as being killed by vampire hunters, being eaten by a dinosaur, and sawing off his own arm then replacing it with a zombie's. These are some of his notable series:Totally Sweet, a series of pop art, large-scale portraits of monsters, each created from thousands of packages of Halloween candy and a single spider. Millikin uses over 40 different kinds of candy, and a single portrait can take between 5,000 and 10,000 candies. Included in the series are portraits of such monsters as Freddy Krueger, Lily Munster, Gort, Godzilla and the Bride of Frankenstein. Millikin compares his artistic technique of building large monsters from many smaller parts to the similar techniques Victor Frankenstein used to create his monster.
Hollywood Witch Trials, a series of painted portraits of celebrities like Paris Hilton and Lindsay Lohan based on their crime mug shots, stylized to look like witches, and combined with excerpts from transcripts of the Salem Witch Trials.
American Mayhem, a series that uses optical illusions to transform the flag of the United States into cityscapes filled with monsters, and incorporates ambigram calligraphy that reads when the paintings are hung upside down. Inverting a national flag in such a way is a commonly used distress signal.
Witches and Stitches, a series of early digital comics, from the 1980s, which were the first webcomics ever published. This unauthorized Wizard of Oz parody comic was published by Millikin on CompuServe as early as 1985 when he was in elementary school. Publishing on Compuserve allowed Millikin to self-publish, avoiding censorship. Witches and Stitches was popular with audiences around the world and Millikin's success inspired many artists to create their own webcomics. Copies of Witches and Stitches are now often difficult to find because Millikin was threatened with a lawsuit over the comic. Millikin's outspoken autobiographical style paved the way for other artists to express their thoughts and opinions on the web.
Literally Impossible, a series of Op art paintings created as answers to questions from a literacy test used to deny voting rights to African-Americans in the American south before the Voting Rights Act of 1965. The paintings feature illusionary impossible objects, ambigrams and palindromes.
Fetus-X, a series of alternative comics created in collaboration with Casey Sorrow. Fetus-X featured a psychic zombie fetus floating in a jar of formaldehyde who may or may not be Millikin's missing conjoined twin or his clone from an alternate timeline or dimension. The comic was run for a short time in Michigan State University's The State News in 2000. After the Catholic League protested the comic and then MSU president M. Peter McPherson declared he wanted it banned, the comic strip was removed for being too controversial. During the controversy over the comic, many people protested on both sides of the issue. The comic was also published in other student newspapers like the University Reporter.
Monkey Day, an international animal rights holiday. Monkey Day (celebrated December 14) was created and popularized by Millikin and Casey Sorrow in 2000 as an opportunity to educate the public about monkeys, as a holiday that supports evolution rather than religious themes, and an excuse to throw monkey-themed art shows and costume parties. For Monkey Day 2012, USA Weekend published Millikin's The 12 Stars of Monkey Day, a series of paintings that were "in part inspired by the many pioneering space monkeys who rode into the stars on rockets, leading the way for human space flight." For Monkey Day 2013, Millikin created a mail art series where he mailed Monkey Day cards to strangers, including Koko the sign-language gorilla and President Barack Obama. In 2014, Millikin debuted a series of monkey portraits using 3D film techniques.
My Drinking Problem, a series of works of endurance performance art, known as "artistic drinking projects." These have included a "Pumpkin Space Odyssey," where Millikin consumed nothing but Pumpkin Spice Lattes for a month, drinking 150 cans of Vernors in just over two weeks for the ginger ale's 150th anniversary, and drinking enough Hi-C to use empty drink boxes effort to brick up his own windows and those of Detroit art galleries.
Millikin's artwork is often shown in galleries and museums. He is one of the artists in the "Out of Sequence: Underrepresented Voices in American Comics" art exhibition which has travelled to the Krannert Art Museum and The Laboratory of Art and Ideas at Belmar, and in the "Monsters of Webcomics Virtual Gallery" at San Francisco's Cartoon Art Museum. His artwork was included, along with Marilyn Manson and HR Giger's, in the international horror art collection "DAMNED."
Millikin also distributes his artwork through college newspapers, in alternative newspapers such as the Metro Times, and in magazines like Wired. His work is also published in major daily newspapers like The Detroit News, Detroit Free Press, The Courier-Journal, The Des Moines Register, The Tennessean and USA Today.
Millikin is known for his political and social activism, with his artwork often tackling controversial issues. He has championed Barack Obama's Patient Protection and Affordable Care Act, commonly referred to as "Obamacare". Millikin has also championed green energy, ridiculing the "Drill, Baby, Drill Brigade" of "oil producers, free-market zealots and global warming deniers."
Millikin has also used his artwork to raise money for causes like helping Hurricane Katrina victims, fighting diseases like muscular dystrophy, and granting wishes to terminally ill children through the Make-A-Wish Foundation. He has also created posters campaigning to raise money for programs to improve adult literacy, auctioned artwork to support soup kitchen efforts to feed the hungry, and created artwork to help people in the city of Flint who had lead contaminated water during the Flint water crisis.
The American Library Association's Booklist describes how Millikin's expressionistic visual style "crosses Edvard Munch with an incipient victim of high-school suicide" and The Hindu describes his paintings as "haunting images." In his book Attitude 3: The New Subversive Online Cartoonists, syndicated newspaper editorial cartoonist Ted Rall describes Millikin's work as "one of the most interesting webcomics around." The Webcomics Examiner named Millikin's comics one of the best webcomics, the webcomics blog ComixTalk named it one of the 100 Greatest Webcomics of all time, and The Washington Post's readers named it one of the top 10 finalists for Best Webcomic of the Past Decade in 2010. Millikin's work has also been nominated for multiple Web Cartoonists' Choice Awards, including their top honor of "Outstanding Comic". Millikin has been a panelist and guest at webcomic conventions, including the inaugural New England Webcomics Weekend, the first convention organized by and focusing on webcomic creators. The Sunday Times described serializer as "high-art", and the Sydney Morning Herald considered them to be the avant-garde. Millikin's artwork is given by Scott McCloud as an example of using the web to create "an explosion of diverse genres and styles" and is described as "mind-blowing" by Comic Book Resources. The Comics Journal has written that Millikin's comics "use the newspaper format for far more daring, entertainingly perverse work" than most comics and is "perfectly at home at a good alternative weekly or a great college paper." The Webcomics Examiner has called Millikin's work "one of the sharpest political commentaries available."
Millikin's artwork has won many awards from organizations including the Associated Press, Society of Professional Journalists, Investigative Reporters and Editors, National Association of Black Journalists, and the Society for News Design. In 2008 his illustrations were part of the series "A Mayor in Crisis", wherein the Detroit Free Press covered, or uncovered, secret text messages of Detroit Mayor Kwame Kilpatrick to reveal the mayor's perjury and obstruction of justice in a police whistle-blower trial. The series resulted in Kilpatrick's being sent to jail and in the newspaper's 2009 Pulitzer Prize for Local Reporting.
His front-page artwork in the Detroit Free Press advocating for U.S. government loans as a solution to the automotive industry crisis of 2008–2009 was described as a "gutsy move" that "stretch[es] the limits of the medium" and CNN's Kyra Phillips described it as "full front page and in your face". Congressman John D. Dingell displayed it on the House floor urging passage of government loans to automakers and reiterated the central theme of the piece, saying "now is the time for us to 'Invest in America'."
Millikin's October 2011 Wizard of Oz-themed Detroit Free Press front-page "Lions, Tigers and Bears: Oh my!" illustration (about the Detroit Lions, Detroit Tigers and Chicago Bears) was praised by ESPN's Mike Tirico during the Monday Night Football half time show.
However, not all criticism of Millikin's artwork has been positive. Since 2000, Millikin has been the target of protest campaigns organized by the Catholic League for what they call his "blasphemous treatment of Jesus". "[Fetus-X] is offensive to Catholics and Christians," Catholic League spokesman Patrick Scully said in August 2002. "It completely ridicules the Catholic faith and is not funny." The Hartford Advocate has called Millikin a "borderline sociopath."