ophie Hall (Amanda Seyfried) is a fact checker at The New Yorker magazine who dreams of becoming a writer, but her boss, Bobby, does not share her wishes. Sophie’s fiance, Victor (Gael Garcia Bernal), is about to open an Italian restaurant in downtown New York. To celebrate, the two go on a “pre-honeymoon” to Verona, Italy. Sadly for Sophie, Victor seems too preoccupied in finding the best wines and cheeses for his restaurant and hardly has time for her. While he is out one day, Sophie goes sightseeing and comes across the house where Juliet Capulet supposedly lived and watches in awe as numerous people gather to write letters to Juliet about their loves and post them on Juliet’s wall. Sophie writes of this in her journal for a few hours and sits on a bench, waiting for closing time, to see what becomes of the letters. A young Italian woman comes to collect the letters, putting them all into a straw basket, and Sophie follows her to a restaurant where the woman meets with three other women, who reveal themselves to be “Juliet’s secretaries”, writing back to each of the letters. The next day, Sophie helps Isabel, one of the secretaries, take the letters. A loose brick falls, and behind it is a crumpled, envelope. Sophie discovers it is a 1957 letter written by Claire, an English woman who while in Italy studying art, fell in love with Lorenzo Bartolini. When he asked her to run away with him, she did not show up and wrote to Juliet about it. Sophie writes back.

A few days later, a young English man arrives. Charlie (Chris Egan) reveals that because Sophie responded his grandmother is now here to find her love. When Sophie asks to meet Claire, Charlie says no, but Sophie follows him and is introduced to Claire (Vanessa Redgrave) who is more than happy to meet “Juliet”. Together, the three decide to embark on a journey to find all the Lorenzo Bartolinis near Siena, Italy where Claire says Lorenzo always enjoyed. The three meet many Lorenzo Bartolinis, but none of them seem to be the right one, as Claire says she’ll be able to see who Lorenzo is through his blue eyes.

Traveling, Sophie and the grandmother and grandson learn about each other’s lives like that Charlie has an ex-girlfriend he hasn't seen in a year, named Patricia, with Claire learning that Sophie’s mother abandoned her when she was nine and Sophie learning that Charlie’s parents died in a car crash when he was ten. Charlie, at first rude, is now attracted to her, but Sophie is standoffish. The three meet many men named Lorenzo Bartolini, including one who has died. Seeing his grandmother cry, Charlie blames Sophie. Claire berates her grandson and tells him about Sophie’s mother, then she visits Sophie in her hotel room and comforts her. Charlie apologizes to Sophie who has gone out and laid down on the grass next to Charlie, and they kiss under the stars.

The next day, while driving back, Claire asks that they stop at a vineyard when she notices it is the vineyard that makes their favorite wine. There, she sees a young Italian man who looks exactly like Lorenzo. Insisting it’s him, Sophie and Charlie go and ask him of his name, which he says is indeed Lorenzo Bartolini. Deciding it must be Lorenzo’s grandson, they ask to speak to the young man’s father, whose name is also Lorenzo. The middle-aged man says his elderly father is also Lorenzo Bartolini, and he was out riding his horse. Charlie urges his grandmother to see if it’s the right Lorenzo, but Claire decides she doesn’t want to. Just then, the elder Lorenzo (Franco Nero) arrives and is indeed Claire’s long-lost love. The two reunite in a heartfelt embrace.

Lorenzo introduces the three to his family. Later, Sophie leaves to go back to Verona and Victor. Claire tells Charlie “not to wait fifty years” before he discovers there is only one girl he loves. Charlie races after her but, seeing her embrace Victor, he leaves.

Back in New York, Sophie presents a story to her boss identical to Claire’s tale, and he tells her he is going to publish it. Excited, she rushes home. The next day at work, she gets an invitation to Claire and Lorenzo’s wedding that Saturday. She breaks up with Victor at the kitchen of his Italian restaurant, and goes to the wedding. At the end of the ceremony, she attempts to talk to Charlie, but believes a woman that is with him, Patricia (Ashley Lilley) is his girlfriend. She hurries away to a balcony, but Charlie follows her. Sophie professes her love but tells him to go back to Patricia, who Charlie explains is his cousin, and not his ex-girlfriend he mentioned earlier. He admits he is in love with Sophie. He attempts to climb up to kiss her like Romeo Montague but falls. Sophie hurries to him and they kiss, Clarie and Lorenzo watched happily and everyone else rushes to see them kiss.