Empire Falls, Maine is a small, decaying and nearly bankrupt town. Miles Roby, the passive and unassuming manager of the Empire Grill, has lived there his entire life. Freshly divorced from ex-wife Janine, who left him for Walt, the owner of the local fitness center, Miles lives in a small apartment above the Grill. Janine, a selfish and cocky exercise addict who has recently lost fifty pounds, lives in Miles' old house with their teenager daughter, Christina ("Tick"), and Walt, who visit the Empire Grill every day in an attempt to show there are no hard feelings about him breaking up Miles' marriage.
Miles' younger brother, David, is a talented cook at the Empire Grill. Their partnership has made the restaurant successful but not profitable due to restrictions by its owner, Francine Whiting, the town's wealthiest citizen. Whiting, who is outwardly friendly but also condescending and manipulative, seems to enjoy exerting control over Miles. She is the widow of C.B. Whiting, who owned the now defunct shirt factory that employed many of the town's citizens, including Miles' late mother, Grace.
Always complicating matters is Miles' grubby ne'er-do-well father, Max, a rascal who can't resist a handout when it comes his way, but nonetheless loves his sons and his granddaughter.
Miles is plagued by flashbacks of his childhood. He recalls a trip to Martha's Vineyard with his mother and their time with a mysterious man named Charlie Mayne. After discovering his father is in jail for being a public nuisance, Miles suspects an affair between his mother and Charlie. When they return to Empire Falls, it's revealed that Grace is pregnant. After being laid off from the shirt factory, she goes to work for Mrs. Whiting, explaining to Miles that she's done someone "a great wrong" and needs to make amends.
As an adult, Miles reflects on these memories and realizes that Charlie Mayne was in fact C.B. Whiting, who after an argument with his wife accidentally ran over their young daughter with his car. The guilt from crippling her led him to exile himself in Mexico, returning years later determined to kill Francine, only to lose his determination at the sight of his daughter and shoot himself instead.
David pushes Miles to stand up to Mrs. Whiting so they can run a more profitable business, which eventually leads to Miles choosing to go into business with his former mother-in-law, Bea, the owner of a local bar. Whiting attempts to sabotage their plans by pulling strings with the county and the police force, culminating in a confrontation with Miles, wherein he quits the Empire Grill and reveals what he knows about his mother's affair with C.B.
Miles is close with his daughter, Tick, who is fending off angry outbursts from her cruel ex-boyfriend, Zack Minty, and an emotional conflict over her mother's engagement to Walt, whom Tick despises. She befriends John Voss, an emotionally disturbed boy at school whose parents abandoned him with his grandmother after years of abuse. The obnoxious jock Zack and his friends constantly bully John. It's eventually revealed as a result of their meddling and cruelty that John's grandmother died months ago and he has been living in her decrepit home ever since.
John comes to the high school with a gun and shoots several of his classmates. He attempts to shoot Tick, but she is saved by the school's principal. Tick is deeply traumatized by the shooting. Miles takes her on an extended trip to Martha's Vineyard, where she begins to recover after several weeks. He calls Janine and discovers that she and Walt split up. A powerful storm caused the nearby river to swell, which led to Mrs. Whiting being killed, removing any remaining impediments to Miles and Bea's new restaurant.
Max arrives in Martha's Vineyard to ask for money and bring Miles and Tick home. Miles suggests that David might not be Max's son, something Max rejects, insisting that, "a man knows his own child," and that David is his son. Max happily reunites with Tick, who says she is ready to return home.
Miles Roby (Ed Harris) – The middle-aged central character of the story. Miles is the seemingly content manager of the Empire Grill in Empire Falls, Maine and is divorced with one teenaged daughter. A blue-collar gentleman with his principles intact, he lives in an apartment over the restaurant he has managed ever since he dropped out of college to look after his dying mother. However, this has left him constantly accountable to Francine Whiting, causing others to persuade him to open a business of his own.
Janine Roby (Helen Hunt) – Miles' ex-wife. She has developed a selfish attitude, damaging her relationship with her daughter and annoying her mother. She gained ownership of the house and custody of their daughter while Miles ended up in an apartment above the Empire Grill. Janine resents the close relationship that exists between father and daughter. As the story progresses, Janine finds that tables are turning on her for the worst.
Christina "Tick" Roby (Danielle Panabaker) – Miles' daughter. She enjoys a loving relationship with both her father and grandfather. Tick is smart, friendly, and more sympathetic than most of her classmates. Her mother's engagement has a negative impact on her. She despises Walt, who is trying to act like a father figure, and resents her mother.
Max Roby (Paul Newman) – Miles' father. Disheveled and constantly defiant of those around him, Max has no problem saying what he thinks of people, even directly to their faces. He is happy to accept any "handout" (or to take anything he wants) even when it means stealing money from the church. Max has a lifelong affinity for Key West, Florida. Despite being a vagabond, Max loves his sons and granddaughter and is a great deal wiser than people assume him to be. (This was Newman's final onscreen role. He is played by Josh Lucas in flashback)
Charlie Mayne (Philip Seymour Hoffman) – A mysterious suitor to Miles' mother and a symbolic figure in Miles' life. Charlie's involvement is pivotal with regard to why Miles has lived in Empire Falls his entire life.
Grace Roby (Robin Wright Penn) – Miles' mother (deceased in present). She considers her son the jewel of her eye. Her affair with Charlie plays a crucial role in Miles' life.
Francine Whiting (Joanne Woodward) – The town's wealthiest citizen. The manipulative Francine holds puppet strings over the town, in particular Miles, and has no problem pulling them when it suits her unscrupulous agenda. Her condescending manner veils a cunning woman with ulterior motives.
David Roby (Aidan Quinn) – Miles' younger brother. A former alcoholic, a reformed marijuana plant grower and a car-crash survivor, David is the chief cook at the Empire Grill. His talent brings a considerable amount of business to the diner. He encourages Miles to take risks, having promised their mother to watch after him. It is also implied that David is actually Miles's half-brother, through flashbacks of their mother and Charlie Mayne.
Walt Comeau (Dennis Farina) – Janine's fiance and the owner of a fitness club. Walt is extroverted and arrogant. He lives with Janine in Miles' old house, trying to develop a fatherly relationship with Tick. Walt makes daily appearances at the restaurant to challenge Miles to an arm-wrestling match. He has a couple of skeletons in his closet, hidden (temporarily) from Janine.
John Voss (Lou Taylor Pucci) – Tick's awkward, introverted classmate. He is from a deprived family, wears ragged, dirty clothing and is known to live with his grandmother after his parents abandoned him. He's constantly ridiculed by Tick's ex-boyfriend, Zack Minty. His history has created a dangerous aura about him, one that eventually escalates. No one but Tick pays enough attention to him until it's too late.
Cindy Whiting (Kate Burton) – Francine's daughter. Despite being permanently disabled by a car accident, she is a sweet woman with high spirits. She has a long-standing attraction to Miles; he is aware of it and is sympathetic but does not feel the same way.
Jimmy Minty (William Fichtner) – A dull-witted, unscrupulous police officer and former classmate of Miles. He is not well liked by most of the town, although he believes he is. Francine keeps him in her pocket by providing perks such as a red sports car. He has an eye on becoming chief of police one day, and unfortunately, has keys to most of the town's businesses which he uses to his advantage. He and Miles ultimately come to blows.
Zack Minty (Trevor Morgan) – Son of Jimmy Minty, Tick's ex-boyfriend and a high school bully. A football star who is an obnoxious and cruel punk, Zack gets away with his bad behavior because of his popularity and his father's status as a police officer. He loves tormenting John to the point of breaking into his house, and is indirectly responsible for making John reach his breaking point.
Bea (Estelle Parsons) – Janine's wise mother. Ex-mother-in-law to Miles, they remain good friends. Bea frequently takes Miles' side rather than Janine's, and often makes rather pointed remarks about Janine's behavior. She owns a local bar and wants Miles to go into business with her.
Charlene (Theresa Russell) – Waitress at the Empire Grill. She is aware that Miles is attracted to her, and she's kind to him, but she is dating David.
Bill Daws (Stephen Mendillo) – The compassionate chief of police and a friend to Miles. He is dying of cancer and is undergoing chemotherapy which takes a heavy toll on his health, confiding only in Miles with the news.
Horace (Jeffrey DeMunn) – A local reporter and a regular patron at the grill. He is an intellectual with a heavy Maine accent and has intimate knowledge of what goes on around town. He has a prominent cyst on his forehead and Max often tactlessly refers to it.
Father Mark (Adam LeFevre) – A friendly priest. He works at a decrepit church, which he has hired Miles to paint.
Father Tom (Nesbitt Blaisdell) – An elderly priest. He is becoming senile and behaves erratically, even helping Max steal money from the church.
Otto Meyer (Larry Pine) – Principal of the high school. A childhood friend of Miles, he is an honorable man who watches out for students like John and Tick. He plays a pivotal role when John "snaps." (Pine also serves as narrator.)
Candace (Delia Robertson) – Tick's classmate and best friend. She finds some amusement when Zack picks on John, but is inevitably involved when John reaches his breaking point.
Justin (Tony Takacs) – Zack's best friend. Overweight, with a penchant for junk food, he participates with Zack in taunting John, although he draws limits when Zack breaks into John's house. He, too, is affected by John's revenge.