Morrison was born in Chicago, Illinois, on April 12, 1979, and raised in Arlington Heights, Illinois. Her father, David L. Morrison, is a retired music teacher who was named "Teacher of the Year" by the Illinois State Board of Education in 2003. Morrison's mother, Judy Morrison, is also a retired teacher. Morrison is the eldest of three children, with a sister, Julia, and a brother, Daniel. She graduated from Prospect High School in 1997, where her parents also worked. She played clarinet in the school's marching band, sang in the choir and was a cheerleader with the school's pep squad. She attended Loyola University Chicago where she majored in Theatre and minored in English, graduating in 2000. She studied with the Steppenwolf Theatre Company before moving to Los Angeles to pursue a career in film and television.
Morrison started her career as a child model, appearing in print advertisements for JCPenney and Montgomery Ward and commercials for Rice Krispies and Mondo. In May 1992, she was featured on the cover of Sports Illustrated for Kids, along with basketball star Michael Jordan.
She made her film debut at the age of fifteen as the daughter of Richard Gere and Sharon Stone in the 1994 film Intersection, and later appeared as Samantha in Stir of Echoes, with Kevin Bacon, in 1999. Her first leading role came in the 2000 film Urban Legends: Final Cut, and she has since gone on to appear in several films, including Grind, with Adam Brody, Surviving Christmas, with Ben Affleck and James Gandolfini, and Mr. & Mrs. Smith, with Brad Pitt and Angelina Jolie, in 2003, 2004 and 2005, respectively.
She has worked on several hit television shows, including Touched by an Angel and Dawson's Creek, before landing the role of immunologist Dr. Allison Cameron on House, M.D., in 2004, co-starring alongside Hugh Laurie, Andrew Airlie, David Anders, Yvette Nicole Brown, Ethan Embry, Skyler Gisondo, Henri Lubatti, Sunny Mabrey, Bailee Madison, Elizabeth Mitchell, Jessy Schram, Rekha Sharma and Rena Sofer. In 2006, she starred in and produced the independent film Flourish. Morrison is also one of the producers that found Glee during its early draft and brought it to attention of writer Ryan Murphy, who, with Brad Falchuk and Ian Brennan, adapted it into a television series. Morrison did not stay involved creatively, but is credited as an associated producer on the first season for her involvement in finding it and helping it get into the right hands.
In 2007, Morrison appeared as Kirce James in the computer game Command & Conquer 3: Tiberium Wars, a character who frequently interacts with the player during the course of the GDI campaign.
Her film projects that year included Big Stan, alongside Rob Schneider, and The Murder of Princess Diana, a television movie based on the book of the same name by Noel Botham. Produced by Lifetime and Working Title Television, Morrison portrays an American journalist, Rachel, who witnesses the car crash which took the life of Diana, Princess of Wales.
In 2009, Morrison returned to the big screen, appearing in the opening scene of J. J. Abrams' Star Trek reboot as James T. Kirk's mother, Winona.
Morrison has also appeared in music videos for Nick Lachey ("Shut Up") and The Donnas ("Too Bad About Your Girl"). She also has appeared on two TV Guide covers with her House, M.D. co-stars, and has been featured in photoshoots with In Style, Stuff, Entertainment Weekly and Premiere, among others. She is currently represented by Abrams Artists Agency. Morrison landed the cover of Health in the 2009 July/August issue.
After her contract on House, M.D. was not renewed, it was announced on December 17, 2009, that Morrison had garnered the role of Kate Keller, Helen Keller's mother, in the Broadway-bound revival of The Miracle Worker. Morrison left her series midway through its sixth season to pursue other projects. However, she did return in another episode in 2010, one directed by Hugh Laurie, to properly wrap up her character's storyline.
In the fall of 2010, Morrison appeared as a guest star in an episode of NBC's Chase. She played the role of Faith, a single mother-turned-fugitive, who embarks on a bloody killing spree across Texas with her daughter in tow. In addition, she has joined the cast of CBS's How I Met Your Mother, as recurring character Zoey Pierson, a mischievous architecture nerd and love interest of main character Ted Mosby, and "the biggest female character we've maybe ever added to the show in Ted's life", according to executive producer Craig Thomas. She later made a cameo appearance in the show's final season.
In 2011, Morrison appeared in Warrior alongside Nick Nolte and Tom Hardy, a film about a young mixed martial artist. Morrison played a mother struggling to keep her family together. In September 2011, Morrison debuted her "starring"" role in ABC's Once Upon a Time. She plays the role of Emma Swan, a bail bonds collector who learns that she is the missing daughter of Snow White and Prince Charming. She holds the key to saving the real and fantasy worlds.
Morrison started dating House, M.D. co-star Jesse Spencer in July 2004. Spencer proposed on December 23, 2006, at the Eiffel Tower. The couple announced in August 2007 that they had called off their engagement. Starting with July 2008, she had been in a relationship with actor Amaury Nolasco. Recently, she's been in a relationship with fellow Once Upon a Time co-star Sebastian Stan (Jefferson).