Bartender follows the nightlife of Ryū Sasakura, a bartending prodigy who is said to mix the best cocktails anyone has ever tasted. Sasakura bides his time in a bar named Eden Hall, hidden in a nook of the Ginza district in downtown Tokyo. It is said that normal people cannot simply find and enter Eden Hall, but they must be invited in by the host. Over the course of the anime, various figures of high and low stature, all of whom share unusual troubles and heavy burdens, are "invited" into Eden Hall and are treated to Sasakura's fine drinks, which, with guidance from the young bartender, lead the customers to reflect upon their lives and decide on a course of action to tackle their problems.
Sato Yo is a high school boy who likes SEGA games. One day, he enters a grocery store to buy some food for dinner. When he tries to take a bento box, he loses consciousness. He comes around to find all the bento sold out. He notices there is a war game going on at grocery stores and players called "Wolves" compete for the half-priced bento. Yarizui Sen, the leader of the Half-Pricer Club, forces Yo to join the club and he enters the bento war.
In the city where Shiki lives, something triggers a spate of mysterious schoolgirl suicides. The connection between the girls who leapt to their deaths is unclear, although all of them have jumped from the Fujou Building, a skyscraper scheduled to be demolished. Meanwhile, Mikiya, after having gone near the Fujou Building, has fallen into a coma. Shiki heads to the Fujou Building herself to save Mikiya. And waiting for her there…is Kirie Fujou. The girls' suicides and Mikiya's coma were all caused by Kirie. Terminal illness had left her bedridden and immobile in a hospital, but one day, she acquires a spiritual body, a separate entity from herself.