Los Angeles bank loan officer Carl Allen finds himself increasingly isolated following his divorce from his ex-wife, Stephanie. Neglecting his friendships with Pete and Rooney, his outlook on life grows progressively bleak. One day, a former colleague introduces him to a "Yes!" seminar, designed to encourage attendees to embrace opportunities by saying "Yes!" after Carl misses Pete's engagement party. An upset Pete confronts him, warning that his current path will lead to profound loneliness. This prompts Carl to attend the seminar, where he encounters the motivational speaker Terrence Bundley. Impressed by Terrence's forceful presentation, Carl commits to saying "Yes!" to every opportunity that arises.
Upon leaving the seminar, Carl finds himself agreeing to help a homeless man, which leads to an unexpected adventure in Elysian Park. He eventually meets Allison, a quirky young woman who provides him with a ride back to his car and shares a fleeting kiss before departing. Inspired by this encounter, Carl’s optimism grows as he takes more risks, despite some humorous setbacks, such as an awkward incident with his elderly neighbor, Tillie. Initially repelled by the idea of intimacy with Tillie, Carl ultimately allows himself to enjoy the moment, leading to a series of transformative experiences.
As Carl embraces this new "Yes!" philosophy, he rekindles his friendship with Pete and Rooney, strengthens his professional relationships, and actively participates in diverse activities—from Korean classes to joining a Persian dating site. His newfound willingness to seize opportunities earns him a promotion at work and enables him to make a significant impact in the lives of others, such as when he plays Third Eye Blind's "Jumper" to dissuade someone from suicide.
When he receives concert tickets from a promoter, Carl is thrilled to discover that the eccentric band he attends features none other than Allison as the lead singer. Their relationship blossoms as they impulsively decide to fly to Lincoln, Nebraska, where they enjoy unexpected adventures together. However, at the airport, federal agents mistakenly profile Carl as a terrorist based on his actions. As the situation escalates, his attorney Pete rushes to his aid, but the stress causes Allison to question Carl's sincerity towards her. Convinced that their relationship may have been a product of his commitments rather than genuine feelings, she chooses to leave.
In a downward spiral, Carl realizes he has neglected important events and friendships while trying to honor his covenant. When the opportunity arises to call Stephanie, he finds himself unable to resist the chance to comfort her, leading to an unexpected kiss. However, when he decisively declines her offer to rekindle their relationship, his life takes an even darker turn, prompting him to reconsider his commitment to the "Yes!" philosophy.
In a dramatic twist, Carl confronts Terrence, seeking release from the covenant, only to end up in a car accident that leads to a hospitalization where he learns that the covenant was never meant to restrict his ability to say "No." Armed with this new understanding, Carl seeks out Allison, expressing his true feelings and desire to take their relationship at a pace he's comfortable with. They reunite, ready to embrace each other with honesty.
In a heartwarming conclusion, the duo is shown donating clothes to a local shelter, demonstrating their shared commitment to making a positive impact in the community. The final moments of the film take a playful turn, showcasing Carl and Allison racing down a hillside in inventive roller suits, a nod to Carl's journey from isolation to connection and adventure.
