Telgemeier was born on May 26 1977, in San Francisco, to parents Denis and Sue. She has two younger siblings, Amara and William. They were ages fourteen (Raina), nine (Amara), and six (Will) when this book takes place. In her pre-teen years, Telgemeier suffered a serious mouth injury that required several years of dental and orthodontic surgery (which is described in her 2010 graphic novel Smile). She was viciously teased by her friends, prompting her to partially withdraw into her love of drawing until she lost her patience when her friends publicly humiliated her. She attended Lowell High School (San Francisco) and eventually found new friends of better character in high school who appreciated her artistic talent, increasing her confidence.

With that encouragement, she studied illustration at New York’s School of Visual Arts (SVA), and graduated in 2002.

Telgemeier was nominated for the 2005 Eisner Award for Talent Deserving of Wider Recognition, and the 2003 Ignatz Award in the categories of Promising New Talent and Outstanding Mini-comic. She was awarded Friends of Lulu’s Kimberly Yale Award for Best New Talent in 2003. She has twice been nominated for the Web Cartoonists’ Choice Award for Outstanding Slice-of-Life webcomic, for her webcomic Smile (A Dental Drama). In 2015, she won the Eisner Award for Best Writer/Artist for her graphic novel Sisters.

In 2004, Telgemeier met an editor from Scholastic at an art gallery party who mentioned that Scholastic was planning to set up a graphic novel imprint (which later became Graphix). At that year’s San Diego Comic-Con, Telgemeier met that editor’s boss, who invited her to pitch an idea for Scholastic. When Telgemeier mentioned she had been a fan of Ann M. Martin’s The Baby-Sitters Club series, they asked her to work up a graphic novel adaptation. Scholastic/Graphix went on to publish four graphic novels in the series: Kristy’s Great Idea, The Truth About Stacey, Mary Anne Saves the Day, and Claudia and Mean Janine. The advances for the adaptations allowed Telgemeier to quit her full-time job and concentrate on her art, and she completed the fourth novel in 2008.

In August 2009, Del Rey Manga released X-Men: Misfits, which Telgemeier co-authored with her then-husband, Dave Roman.

At the same time, Telgemeier was invited to join Girlamatic, a subscription-based webcomics site with an emphasis on stories for young women. The disciplined structure and schedule of publishing a weekly webcomic encouraged Telgemeier to develop the autobiographical story that would later be published in 2010 as Smile. By the time she had completed work on the Babysitters Club adaptations in 2008, she had developed a substantial amount of Smile and received encouragement from Scholastic to continue work.

In February 2010, Telgemeier released Smile, which reached The New York Times bestseller list in 2011 and remained on the list for over 220 weeks.

Smile, her graphic novel based on her webcomic, is a 2010 Boston Globe-Horn Book Award Honor title. This is the first time a graphic novel has been nominated for or won this award. Smile was a 2010 New York Times Book Review Editor’s Choice, a Kirkus Reviews Best Book of 2010, a 2011 ALA Notable Children’s Book, a 2011 YALSA Top 10 Great Graphic Novels for Teens pick, and a Children’s Choice Book Award Finalist. In 2011, the book won the Eisner Award for Best Publication for Teens.

In September 2012, her graphic novel Drama about a middle school stage crew and performers, was released. Although the novel was fictional, it drew on experiences from Telgemeier’s experience in middle school and high school theater.

In August 2014, her second autobiographical graphic novel, Sisters, about her life growing up with her younger sister, was released.

On May 10, 2015, four of Telgemeier’s books (Drama, Smile, Sisters, and Kristy’s Great Idea) were the top four on The New York Times Best Seller list for paperback graphic books.

In September 2016, Ghosts was released, which is about a girl and her family moving to a new town. The girl is able to see ghosts and some events in the novel are set in late October, when the town is celebrating the Day of the Dead. Telgemeier stated she had been developing Ghosts since 2002.

In September 2019, Guts was released, about Telgemeier’s stomach problems and her adventures in food, school, and changing friendships. In 2020, she received the Eisner award for Best Writer/Artist, for her graphic novel Guts.