Telgemeier was born May 26, 1977 in San Francisco. In her pre-teen years, Telgemeier suffered a serious mouth injury that required several years of dental and orthodontic surgery. In addition, she was also viciously teased by her friends for this medical treatment, prompting to her to partially withdraw into her love of drawing until she lost her patience with the abuse when they publicly humiliated her. She 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, and currently lives in Queens, New York. She lists Jeff Smith, Lynn Johnston and Adrian Tomine among her influences. She is married to Dave Roman, who is also a cartoonist.

Telgemeier's works include a series of self-published mini-comics called Take-Out, a short story in Bizarro World for DC Comics, a short story in Volume 4 of the Flight anthology,and four graphic novel adaptations of Ann M. Martin's The Baby-sitters Club series for Scholastic/Graphix: Kristy's Great Idea,The Truth About Stacey, Mary Anne Saves the Day and Claudia and Mean Janine.

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

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 Smile.

The Baby-Sitters Club Graphic Novel Kristy's Great Idea was picked by YALSA for their 2007 Great Graphic Novels for Teens list, as well as ALA ’s Booklist 2007 Top Ten Graphic Novels for Youth list. ALong with one of her most popular, Smile

Smile 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.