Irish Catholic Mickey Fitzpatrick is a New York City taxi driver, unhappy over an act of infidelity committed by Heather, his ex-fiancée. His brother, Francis, is a Wall Street stock investor married to Renee, though she is frustrated by his lack of desire for sexual relations – not knowing that he is in a heated affair with Heather.
During weekends, Mickey and Francis visit their parents' home on Long Island. Their father, Frank, is locked in old-school low-key sexist ways, who is always telling Mickey and Francis what to do, yet also advises them to always go for what drives them to succeed.
Driving his cab, Mickey picks up Hope, an NYU art student headed to the airport. They click within seconds and she asks him to drive her to New Orleans. They become infatuated and impulsively marry the next day, returning to New York two days later to tell Francis and Renee. Francis is upset, mostly because he was not asked to be best man. Mickey moves in with Hope, but later becomes disillusioned with her bohemian lifestyle, including frequent power cuts in their ramshackle apartment. Francis grows concerned that he is being unfair to Heather by continuing to stay with Renee. At the same time, Renee's Italian-American family, mostly her younger sister Molly, suggest the problem with Francis' lack of interest in her is that he may be gay, so she asks Mickey and Frank to confront him. He denies being gay, but admits to being unfaithful.
Francis belittles Mickey for the lack of forward progress in his life with Hope. Francis also argues with Heather about her ongoing sexual relations with a wealthy old man referred to as "Papa". When Mickey picks up Heather as a fare, he goes up to her apartment to retrieve a television that belonged to him during their relationship. When she implies that he wants more than the tv from her, he does not reciprocate, instead chastizing her for the infidelity that ended their engagement and for her time as a call girl to pay her way through college. Throughout all this, Frank offers more egotistical advice to them—only to be devasted when he learns, during a fishing trip with his priest, that his mutually religious wife hasn't been to Mass in months.
On a visit to Heather's apartment, Francis learns about her meeting with Mickey. Francis shows up at his brother's apartment to question him about whether or not Mickey had sex with her. Later, Mickey discovers that she is the woman Francis is having the affair with. The revelation escalates to an argument at their parents' home, leading Frank to strap boxing gloves on them, with Mickey winning on the first punch.
Francis finally confronts Renee with his affair and files for divorce. When Mickey finds out he intends to marry Heather, he informs Francis of Heather time as a prostitute, causing Francis to get cold feet.
Hope informs Mickey that they will need to move to Paris in a month if she is accepted into an art school there. Mickey is already unsure about whether to join her when he meets Connie, Hope's co-worker at a neighborhood bar, who claims to have had a "special relationship" with Hope before the marriage. Mickey reacts poorly, leading Hope to tell him that she is unsure if he should come to Paris after all.
Due to Francis' sudden indecision over marriage, Heather decides to marry Papa. When Francis threatens to tell Papa that Heather was a prostitute, Heather tells Francis that Papa was "her best customer". He then calls Renee in hopes of getting back together with her, but she is already in a relationship with Scott Sherman, a family acquaintance whom Francis previously observed was a fatso geek, while Renee had pointed out that he was shy and sweet and nicer than Francis.
Mickey and Francis meet with Frank at his house, where their distraught father tells them that their mother left the previous day for a hardware store owner she has been sleeping with when supposedly at church. Frank apologizes to Mickey and Francis for giving them bad advice about life and love when his own wife was cheating. The three men decide to go out fishing aware that despite the failure of their love lives, they will always have each other. As they prepare the motorboat to cast off, Mickey realizes he must try to talk with Hope before she leaves for Paris. Mickey is surprised to learn that Frank has arranged a special guest – Hope. Hope asks to drive the boat, but Frank, who never allowed a woman on his boat before, says it is too soon for that.
Critical reception of the film was positive. Review aggregation website Rotten Tomatoes gives the film a score of 61% based on reviews from 51 critics, with an average rating of 5.8/10. Critics were, overall, won by the performances of John Mahoney, Jennifer Aniston and Cameron Diaz: Aniston and Mahoney brought a "kind of solid professionalism" according to Janet Maslin and Lisa Schwarzbaum. Chris Hicks said, "Better, however, are Diaz, lending charm to a character who could have been quite unsympathetic, and especially Aniston, whose decent, trusting character is quite appealing. Best of all, however, is John Mahoney, hilarious as the bombastic patriarch of the Fitzpatrick clan, who refers to his sons as 'sisters' and calls them 'Barbara' or 'Dorothy' while offering ill-advised sarcasm in place of fatherly wisdom." For Louise Keller, "Burns, Diaz, Bahns and Aniston inject an energy and charisma of their own, and they're fun to watch." Paul Fischer found that Diaz and Aniston are "both in fine form". Alison Macor said, "As Francis' wife Renee, Aniston provides one of the few bright spots in She's the One. Playing Renee as the wry voice of sanity among the rest of the characters, Aniston shows that she's the one who makes this film somewhat enjoyable."
Critics were less forgiving of Maxine Bahns. Mick LaSalle said about her, "The graduate student, Hope, is played by Maxine Bahns, Burns' real-life girlfriend, who was also his love interest in McMullen. Throw a rock out the window, and it's sure to hit someone with more acting talent than Bahns. She can't say a line without it ringing false and keeps smiling nervously, like a shy person at a party. In a way, it's rather sweet that Burns keeps casting Bahns. But She's the One would have been much improved had Burns given Jennifer Aniston the Bahns role. Instead Aniston is wasted here as the unloved wife of Mickey's callous brother, Francis (Mike McGlone of McMullen). She looks great, but all she gets to do is whine and smoke, and she all but disappears two-thirds of the way into the film."
The music for the film was composed by Tom Petty, and performed by Tom Petty and the Heartbreakers. The accompanying soundtrack album leaves out most of the instrumental music featured in the film, and includes a number of songs that are not in the film, or are only heard playing dimly in the background. Many of the songs were written (and some recorded) for Petty's 1994 success Wildflowers. Singles released from the soundtrack included two versions of the song "Walls" (featuring Fleetwood Mac's Lindsey Buckingham), "Climb that Hill" and a song written by Lucinda Williams, "Change the Locks". The album also included a cover of "Asshole", a song by Beck.
In 2000, Fox Home Entertainment released "Stories From Long Island: Three Films by Edward Burns" ($70), a DVD set which included The Brothers McMullen (1995), She's the One and No Looking Back (1998)."