Happiness for Beginners opens with Helen Carpenter dropping off her dog, Pickle, to be looked after by her brother, Duncan. Duncan has forgotten his promise, however, and Helen arrives at his Boston apartment to discover that a raging party full of college students is underway. In Duncan's room, she speaks with his roommate, Jake, who she has known for six years and has always dismissed as being exactly like her irresponsible brother. Helen learns that Jake is going on the same Back Country Survival Company course as her, and he asks for a ride to Wyoming. Helen is reluctant to have him tag along on what is supposed to be a regenerative, spiritual trip for her, but she agrees when he says he will have to hitchhike otherwise.
Helen and Jake take turns driving to their first stop, the home of Helen's grandmother GiGi in Evanston, Illinois. GiGi is out, but has left wine and pasta for them. Jake beats Helen at a game of Scrabble; Helen agreed to give him a kissing tutorial if she lost. They are interrupted before they can kiss. Sexual tension builds throughout the next day on the road, and they finally make out at a motel they stay at. Helen realizes Jake didn't actually need a tutorial in kissing, but she is happy he tricked her.
As Helen initiates sex, her ex-husband phones twice. She reluctantly answers and talks him through a near relapse. They have been divorced for a year because Helen miscarried and Mike wasn't there to support her because he was on a bender. A recovering alcoholic now, he continues to cross boundaries with Helen and rely on her for emotional support. After an hour on the phone, Helen tries to start things up with Jake again, but he tells her she deserves a man who is less selfish than he and her ex.
Helen stews in resentment as they drive to the BCSC headquarters. Before joining the hike, she asks Jake to pretend that they are strangers once the program starts. Jake reluctantly agrees. They join the group, which comprises mostly college-age people like Jake, and Helen feels out of place being a decade older. Helen decides to forget about Jake and focus on the reason she joined the hike: to subvert people's expectations of her and earn a Certificate of Merit, which will confirm for her that she has bounced back from her failed marriage.
Jake quickly earns the respect of the group, able to relate to the guys and charm the women. Helen is one of the slowest hikers and the instructor, Beckett, continually uses her as an example of how not to do things in the wilderness. The highlight of her first week is talking with Windy, an attractive Californian who talks about positive psychology and gives her advice about how to relate better to her traumatized dog. However, Windy reveals that she has a crush on Jake, leading Helen to unfavorably compare herself to Windy.
Helen earns the respect of Beckett and the group when she hikes solo in order to get help for Hugh, a guy who breaks and dislocates his hip after stepping through a rotten log. On a rest day in a beautiful area known as the Painted Meadow, Helen connects with nature and works through the guilt and resentment she carries from when her brother Nathan died by drowning. Though she is impressing Beckett with her initiative and acquisition of survival skills, and accomplishing most of the goals she went into the trip with, Helen nonetheless continues to worry about Jake and Windy's growing intimacy, which is the subject of gossip from other hikers.
One night, Jake loses his glasses while gathering water from a ravine. He admits to Helen that he has been hiding the fact he has a vision disorder that means he will soon be completely blind. After she talks through it with him and finds his glasses, Jake kisses her passionately. When he stops, Helen believes it is because he is with Windy now.
At the end of the hiking trip, the group votes on which three hikers have earned a Certificate of Merit. To Helen's chagrin, they go to Jake, Windy, and Hugh. However, she learns that Beckett gave her his two votes. She leaves Wyoming believing Jake is going to drive with Windy to his father's place in Colorado. Helen stops again in Evanston, where Duncan arrives with Pickle's dead body in a cooler. He explains that she died in his arms of a gas bubble that got trapped in her intestines. Having talked with her grandmother about her resentment of Duncan being related to her guilt over Nathan's death, Helen is able to forgive Duncan and accept him as somewhat incompetent but ultimately well-meaning.
Helen and Duncan go to a bar mitzvah being thrown for the child of her high-school boyfriend, who cheated on her with her former best friend. At the party, GiGi arrives with Jake. Jake catches Helen on her way out and admits he came back for her, having rejected Windy once he realized she wanted to be with him. The two become stuck in the hotel's elevator and are forced to talk through everything.
Jake admits to his shame over his eye condition: he believes it is immoral to pursue a relationship with Helen when he knows he will go blind soon and rely on her support more than most partners. Helen confesses she is in love with him too, and doesn't see his condition as a reason not to pursue a life with him. The book ends with the couple being freed from the elevator and taking the stairs up to the room Jake has rented at the hotel.
