After he graduated from high school, Rosen chose to go to Kent State University for a year before transferring into the pre-med program at Ohio State University. He finished up as an animal behavior major in 1976 and attended St. George's University School of Medicine in Grenada for a short time before going on to work as an instructor for Ohio State University through 1985. During that time, he also attended Columbia University, earning his Masters in poetry in 1981.

After getting his MFA in poetry, Rosen started work as a design consultant for the Jefferson Center for Learning and the Arts in 1982. In 1983, he became the literary Director of the Thurber House in Columbus, Ohio. During his near-twenty-year stay as literary Director, Rosen was the Editor for several compilations of James Thurber's writings; he also was involved in the creation of the Thurber Prize for American Humor. Rosen has also "taught in the Ohio Art Council Poetry-in-the-Schools Program and Greater Columbus Arts Council Artist-in-the-Schools Program, and has conducted over 500 young authors' conferences, in-service days, writing workshops, guest author days, and residencies (for elementary, middle school, and high school students and teachers)."

Michael J. Rosen is a very prolific author who has been involved in the creation of over 150 books. He first began his career as an author in 1984 with the publication of a book of poetry called A Drink at the Mirage. Rosen has written on a wide variety of topics, ranging from children’s books on religion (Our Eight Nights of Hanukkah; The Blessing of the Animals) to books about dogs (With a Dog like That, a Kid like Me... ; The Company of Dogs: Twenty-one Stories by Contemporary Masters) to humorous fact books on various subjects (No Dribbling the Squid: Octopush, Skin Kicking, Elephant Polo and Other Oddball Sports; Balls!; The 60-Second Encyclopedia). Some of his most popular works include his most recent book Any Body's Guess!: Quirky Quizzes About What Makes You Tick, Mirth of a Nation: The Best Contemporary Humor, 101 Damnations: The Humorists' Tour of Personal Hells, The Cuckoo's Haiku, and Elijah's Angel: A Story for Chanukah and Christmas. Rosen says of his ideas on writing, "A story must be a real enough house so that you can walk around, get comfortable, grab something from the fridge, and then be surprised by the ideas that haunt the place."

Rosen also established his own granting program, The Company of Animals Fund, in 1990; the program "offered support to animal welfare agencies providing emergency or ongoing care to companion animals from the profits of seven books and two touring illustration exhibits." The fund was benefitted by "three anthologies of short stories, collections of commissioned personal essays and visual suites, children's books, and sidelines such as boxed cards and illustrated address books." Rosen has been quoted in an interview saying "It has been an enormous honor to precipitate such collections and a concomitant reward to know that these generated funds offer such lasting benefits. Rather than imagine this a unique design, I hope that such collective philanthropy becomes a perennial enterprise in publishing."

Elijah's Angel: A Story for Chanukah and Christmas is a multiple award-winning tale about the friendship between a 9-year-old and an 80-year-old barber. The book's title character is based on Elijah Pierce, a barber nearby to whom both Rosen and the book's Illustrator Aminah Robinson lived. Among other honors, the story has received the National Jewish Book Award (1993), has been named an American Bookseller's Pick of the Lists, was designated by Parents' Magazine as the Best Book of 1992, and was the inspiration for a family opera by Composer Robert Kapilow. Ari L. Goldman of The New York Times called the book "so finely done that the drawings and the story line compete for attention."

Mirth of a Nation: The Best Contemporary Humor, originally published in 2000, is an anthology of contemporary humor written by over fifty comedians, Writers, and other funny fellows, and edited by Michael J. Rosen. Mirth of a Nation was reviewed positively by January Magazine, a review in which Jonathan Shipley said that “Michael Rosen, author and Editor of many notable books for adults and children as well as the literary Director of The Thurber House, has collected some funny writing. Seriously, it's good stuff.” When interviewed, Michael J. Rosen said that “Mirth... and More Mirth of a Nation make another claim: That humor writing is seriously funny. Now of course I mean "genuinely" funny, but I also mean also "seriously" as in "profound" — humorists are among the few dependable sources of honest (re)calibration and reality checking.” The volume was later published in 2002 as an audiobook, and in 2007 in hardcover format. Rosen also edited two additional humor anthologies in the same vein, More Mirth of a Nation (published November 2002), and May Contain Nuts (published September 2004).

In 2013, Rosen was commissioned by the Jewish Community Center of Greater Columbus to create a full-length play based on this work. Its world premier will be staged at the Center's theater in December, 2013.

Michael J. Rosen was named by The New York Times as "an Example of creative philanthropy". Rosen has served on the board of Directors for Share Our Strength for over fourteen years; the profits from six of the books he has created benefit the organization, including two cookbooks with recipes from over one hundred and fifty of the United States’ most esteemed chefs. In 2005, his efforts were recognized by the organization with its first Lifetime Achievement Award. In an interview by ABCDBooks about Down to Earth, Rosen explained that learning about Share Our Strength was like seeing "a door where before I had perceived a wall. It takes all kinds of people with all sorts of talents to address any cause we might face."