Harris was born in Daytona Beach, Florida and grew up in Queens, New York, raised by her single mother, Fran. She has a sister, Ashley. Harris is Jewish. In 1995, she was stalked by an obsessed fan, Christopher Small, who wrote letters threatening to kill her. Small was later arrested after bringing a shotgun and a teddy bear to her home. On January 29, 2007, Harris appeared on an episode of The Dr. Phil Show recounting the terrifying experience. The stalker was obsessed with her character Molly on the TV show Roseanne. In October 2009, Harris was granted a restraining order against Small, who began sending her messages on Twitter. The restraining order will expire in 2012.

Danielle's family moved to Port Orange, Florida when she was in the fourth grade, where she attended Spruce Creek Elementary School. However, her tenure there was short-lived after winning a children's beauty contest which took her to New York. When in New York, Harris began her professional career by appearing in television commercials while maintaining an A average at PS 117 and PS 232 in Queens, New York.[citation needed] Her first acting role soon followed in 1985, when she made her debut as Sammi Garretson on ABC's One Life to Live, a role she played for three years.

In 1988, she auditioned & beat out Melissa Joan Hart for the part of Jamie Lloyd (Michael Myers's niece) in the movie Halloween 4: The Return of Michael Myers. Just one year later, she would reprise the role in Halloween 5: The Revenge of Michael Myers. The character of Jamie returned in 1995 for Halloween: The Curse of Michael Myers, but Danielle did not participate due to disagreements on her fate in the script.[citation needed] Also, Harris requested $5000 to appear in the film (far less than she was paid for Halloween 4), but no agreement could be reached.[citation needed] J.C. Brandy ended up playing Jamie in the film, a decision with which some of the fans of the Halloween series were dissatisfied.[citation needed] Harris would later return to the franchise in a new role, that of Annie Brackett, in Rob Zombie's Halloween, a 2007 re-imagining of John Carpenter's 1978 original. In the 2007 remake, she had nudity for a sex scene and her victimization, which caused controversy.[citation needed] She stated "I want people to see me in this movie as Annie Brackett, not Jamie. I'm not little Jamie anymore and people need to realize that." She reprised her role in Rob Zombie's Halloween II, released on August 28, 2009.

Harris's other film credits include Marked for Death (1990) alongside Steven Seagal, Don't Tell Mom the Babysitter's Dead (1991) alongside Christina Applegate, City Slickers (1991), The Last Boy Scout (1991) alongside Bruce Willis and Damon Wayans, Free Willy (1993), Daylight (1996) alongside Sylvester Stallone, Wish Upon a Star (1996) alongside Katherine Heigl, and Urban Legend (1998). She has also appeared frequently on television, with a recurring role on the sitcom Roseanne during the 1992-93 season (as Roseanne's neighbor Molly), and subsequent guest appearances on Boy Meets World, Diagnosis Murder, Charmed, ER and Cold Case. As well, she appeared in a season four promo for American's Funniest Home videos. She also appeared alongside Ellen Burstyn for two years on the CBS drama That's Life, and as the voice of Debbie Thornberry on the animated series The Wild Thornberrys, which ran for five seasons, and as the voice of Sierra, the adolescent lioness in the short-lived animated series Father of the Pride.

Some of Harris's most recent projects include the films Debating Robert Lee, Race You to the Bottom (an Outfest prizewinner) and the upcoming Left for Dead, as well as an appearance in the music video for the song "The Bleeding", by Five Finger Death Punch. She also stars alongside Lance Henriksen, Bill Moseley, AFI's Davey Havok, and Battlestar Galactica's Nicki Clyne in the "illustrated film" series Godkiller. She hosted Route 666: America's Scariest Home Haunts on FEARnet.

Her films Godkiller and Blood Night saw DVD releases in late 2009. Fear Clinic, a FEARnet.com original webseries, co-starring Danielle and Robert Englund, Kane Hodder, and Lisa Wilcox, will debut around Halloween 2009, as well as Danielle's own horror website, horrorgal.com. In November of that year, she was featured as a guest-vocalist of Danish rock band Cryoshell's cover of "Creeping In My Soul" by Christine Lorentzen (who is also the lead vocalist for the band). She can also be seen as Felicia Freeze in Super Capers, and will appear with Robert Patrick in the upcoming The Black Waters of Echo's Pond. She is currently shooting Jim Mickle's second feature film the vampire flick Stake Land, due in 2010 and Night of the Living Dead: Origins 3D who is directed by Zebediah de Soto. On Dec. 3rd Harris confirmed a role in the horror film "Hatchet 2", where she portrays Marybeth. Harris is a guest star of the 2010 Creation Entertainment Weekend of Horrors in the Marriott Los Angeles Airport on 21 May 2010. She appears in the upcoming vampire thriller New Blood.

Danielle has posed for a photo shoot and been interviewed in GoreZone Magazine issue#57. She is featured on the cover nude save for a pair of boyshorts although she covers herself.