Based on Toby Young's memoir of the same name, How to Lose Friends & Alienate People follows the story of a British writer, Sidney Young, who lands a job at a prestigious magazine called Sharps in New York City. Sidney is initially thrilled to be given this opportunity but quickly realizes that fitting in at the magazine is harder than he thought.
Sidney's lack of understanding of American culture and customs causes him to inadvertently offend people at the magazine, and his tendency to speak his mind rubs his coworkers the wrong way. His unconventional approach to journalism (he once wrote an article comparing orgasms to the September 11 attacks) only adds fuel to the fire.
Sidney's struggles continue as he tries to make a name for himself at Sharps while also pursuing a romantic relationship with Alison Olsen, a coworker whom he has a crush on. Along the way, he finds himself caught up in the egos and power struggles of his colleagues, including the magazine's editor-in-chief, Clayton Harding, and rising star Sophie Maes.
As Sidney's missteps pile up, he begins to question whether Sharps is the right place for him and whether he even wants to fit in with the people there. In the end, he must decide whether to conform to the culture of the magazine or forge his own path in the industry.