Burke was born in Fort Lauderdale, Florida, but was raised primarily in Wichita, Kansas, where her mother was a school librarian and her father, fellow mystery novelist James Lee Burke, was a professor of English. She traces her fascination with crime to BTK, a serial killer who was active in Wichita during the 1970s.

Burke received her B.A. in psychology from Reed College, completing the senior thesis "Emotion's effects on memory: spatial narrowing of attention". After graduating with distinction from Stanford Law School, she served as a deputy district attorney in Portland, Oregon, where she prosecuted domestic violence offenses and served as an in-precinct advisor to the police department. She currently lives in New York City and is a Professor of Law at Hofstra Law School. She is a member of the board of directors of the Mystery Writers of America and currently serves as President of its New York chapter.

Burke's novels are known for their authenticity and often draw on real-world cases and the author's own personal and professional experiences.

Burke's Samantha Kincaid series is set in the Multnomah County District Attorney's Office, where Burke worked in the 1990s.In creating NYPD Detective Ellie Hatcher, Burke drew on her experience growing up in Kansas. Like Burke, Hatcher was raised in Wichita. Hatcher's father was a Wichita police detective who spent his career hunting a serial killer who evaded police for thirty years.

Burke's first novel, Judgment Calls, was loosely based on the case against Keith Hunter Jesperson, a serial killer known as the Happy Face Killer for the smiley faces he drew on his many letters to the media. Burke's novel, Angel's Tip, was loosely based on the murders of Imette St. Guillen and Jennifer Moore.

In Burke's novel, Dead Connection, Ellie Hatcher tracks a serial killer who uses an online dating service to locate his victims. Burke has said that the plot was inspired by her worst nightmares while briefly enrolled on Match.com. Burke subsequently dedicated the book to her husband, writing, "For Sean, I can't believe I found you on a computer."