Moynahan was born in Binghamton, New York, the daughter of Irish American parents Mary Bridget (née Moriarty), a former school teacher, and Edward Bradley Moynahan, a scientist and former administrator at the University of Massachusetts Amherst. She has two brothers, Andy and Sean. Her family moved to Longmeadow, Massachusetts when Moynahan was around seven years old, where she later attended Longmeadow High School, and was captain of the girls' soccer, basketball, and lacrosse teams, graduating in 1989. She has said that, during her childhood, she was a tomboy.
After graduating from high school, Moynahan pursued a modeling career despite admitting she had never read fashion magazines growing up. She had accompanied a friend to a modeling audition in Springfield, Massachusetts, and was signed by the modeling agency instead of her friend. She began her career appearing in department-store catalogs in Springfield, during which time she attended the University of Massachusetts Amherst.
Moynahan moved to New York at age 18 and, a year later, began appearing in magazines such as Vogue and Elle, and on covers of other widely known magazines. Her cover highlights include Vogue Paris (May 1993), Elle (October 1993), and Glamour (six times). In an interview given in July 2004, Moynahan, discussing her early work, said: "It was a crazy world that paid a lot of money. I liked being a model, but I knew it would never last, so I looked into acting."
During that time, she began doing soap and shampoo commercials, in addition to taking acting and art classes. She studied acting at the Caymichael Patten Studio in New York, and in 1999, made her television debut as Natasha in HBO's romantic comedy Sex and the City. She later had a recurring role in the show, until the divorce of her character from Mr. Big (Chris Noth). The following year, she appeared in smaller film roles, including parts in In the Weeds and Whipped.
Moynahan made her feature-film debut in the 2000 comedy-drama Coyote Ugly as Rachel, a bartender/dancer in a wild New York bar, a role that is considered Moynahan's breakthrough. She had accepted the role because she "thought it was interesting that the whole movie revolved around five women...and my character was so strong and independent". The film garnered generally unfavorable critical reviews, but was a box-office success, earning $133 million worldwide. Her next role was a supporting role in 2001 film Serendipity as Hally, the fiancée of John Cusack's character.
Moynahan was then cast opposite Ben Affleck and Morgan Freeman in the action film The Sum of All Fears, based on Tom Clancy's book of the same name. Moynahan plays Dr. Catherine Muller, a strong, independent woman, and love interest for Affleck's Jack Ryan. Dave Larsen of the Dayton Daily News reported that the subplot involving Moynahan and Affleck was "the film's weakest point". The Sum of All Fears received ambivalent reviews, but was a commercial success, earning $193 million at the box office. Her next role was as a CIA trainee in The Recruit (2003). The movie was not well received, with Mike Clark of USA Today commenting that The Recruit is "less-than-middling melodrama whose subject matter and talent never click as much as its credits portend".
In 2004, Moynahan starred alongside Will Smith in Alex Proyas' science-fiction movie I, Robot, loosely based on Isaac Asimov's short-story collection of the same name. Moynahan portrays Dr. Susan Calvin, a specialist in robot psychology. Upon release, I, Robot received mixed reviews, though critics enjoyed Moynahan's performance. Daniel Neman of Richmond Times-Dispatch, who disliked the film, concluded that she "turns in an able performance as Dr. Calvin, the convenient character." With revenue of $347 million worldwide, the film remains Moynahan's most commercially successful picture to date. Her next movie was in 2005's Lord of War, a political crime thriller, as Ava Fontaine Orlov, the wife of Nicolas Cage's character. In 2006, Maxim named her number 96 on its annual "Hot 100" list.
In September 2006, away from film, Moynahan starred as Whitney Crane in the ABC television drama series Six Degrees, co-starring alongside Jay Hernandez, Erika Christensen, Hope Davis, Dorian Missick, and Campbell Scott. The series centered on six residents of New York City and their respective relationships and connections with one another, based on the idea of six degrees of separation. It debuted on September 20, 2006, and was watched by almost 13.3 million viewers. Six Degrees debuted to varied reception, with David Hinckley of the New York Daily News writing, "In theory, it's an intriguing concept for a series. But in practice, Six Degrees doesn't work at all in drawing you in at the start." The series was cancelled after one season in May 2007.
Moynahan's next film role was in the November 2006 thriller Unknown, about a group of individuals kidnapped, and trying to work together how to escape from their captors. She was next seen in 2007, in Gray Matters, starring alongside Heather Graham and Tom Cavanagh, before being cast in Henry Bean's comedy-drama Noise, as Helen Owen, the wife of David Owen (Tim Robbins). The movie was screened at a special presentation at the 2007 Rome Film Festival and was released in theaters in 2008.
In December 2008, Moynahan guest-starred in two episodes of the ABC television comedy-drama Eli Stone, playing the titular character's (Jonny Lee Miller) former girlfriend. Returning to film, as the last feature she starred in was 2007's Noise, Moynahan appeared in Ramona and Beezus, playing the mother to Joey King and Selena Gomez's characters. The film was directed by Elizabeth Allen and released in July 2010. The following year, Moynahan starred alongside Aaron Eckhart, Michelle Rodriguez, and Michael Peña in the action science-fiction feature Battle: Los Angeles (2011). Away from film, Moynahan stars in the CBS television drama Blue Bloods, playing Assistant District Attorney Erin Reagan.
In November 2009, she signed a deal with Garnier to appear in television and print advertising promoting their skincare products (Ultra-Lift).
Moynahan was in a three-year relationship with screenwriter Scott Rosenberg. She dated NFL quarterback Tom Brady from 2004 until December 14, 2006. Her representative confirmed their split to People in December 2006, stating that they had "amicably ended their three-year relationship".
On February 18, 2007, Moynahan's representative confirmed to People that she was more than three months pregnant, and that Brady is the father. On August 22, 2007, she gave birth to a baby boy, John Edward Thomas Moynahan. In a July 2008 interview in Harper's Bazaar, Moynahan discussed her willingness to raise her son as a single mother. Despite media reports that Moynahan and Brady have an acrimonious relationship, it was revealed that the two have maintained a civil relationship since the birth of their son.
Moynahan resides in Pacific Palisades, California. She began dating director Joseph McGinty (McG) in late 2010. On October 17, 2015, she married businessman Andrew Frankel at a ceremony in the Hamptons.Moynahan, Bridget; Goldberg, Wendy; Peterson, Chris (2015). The Blue Bloods Cookbook: 120 Recipes That Will Bring Your Family to the Table. New York: St. Martin's Press. ISBN 9781250072856. OCLC 918562873. Retrieved February 6, 2017.