The Assistant tells the story of an immigrant grocer, Morris Bober, who lives and works in Brooklyn, New York. Bober emigrated from Russia in his teenage years and met his wife Ida in New York. Their grocery recently has fallen on hard times because a new store has opened across the street and is taking their customers. To stay afloat, the Bobers also rely upon the wages of their daughter, Helen who works as a secretary.
On the opening day of the novel, two men rob Morris's grocery and knock him unconscious with a blow to the head. Following his injury, a man named Frank Alpine arrives in the neighborhood. Frank has come from a rough life in the West to start again. When Morris re-opens the store, Frank appears each morning to help him drag in the heavy milk crates. Eventually, Frank asks if Morris would let Frank work for free so that Frank could learn the trade. Morris says no and Frank disappears. Soon after Morris observes that a quart of milk and two rolls are stolen from his deliveries each morning. After a week, Morris alerts the police because he cannot find the culprit. On the next day, Morris finds Frank Alpine sleeping in his cellar. Frank admits to stealing the milk and bread out of hunger. Morris feeds Frank and lets him sleep in the grocery for the night. The next morning, Morris slips while dragging in the milk and passes out. Frank rescues him then puts on the grocer's apron and starts working in the store.
During the two weeks that Morris recovers, Frank manages to bring in much more money than Morris had done. When Morris returns, Frank moves upstairs to a small room off an apartment that an Italian couple, the Fusos, rent. Because business is so successful, Morris eventually wants to pay Frank. Frank feels guilty about being paid because unknown to the grocer, Frank has been stealing money. Furthermore, it was he and Ward Minogue, a boy whose father is a local detective, who had robbed the grocery.
Frank becomes interested in Helen Bober. Helen recently lost her virginity to Nat Pearl a local Jewish boy whose parents own a candy store and who is attending Law School, but she shunned him after learning that he only wanted sex. The other local Jewish boy on the street, Louis Karp, suggests that Helen marry him, but she is not interested. Frank courts Helen by meeting her at the library, which she visits twice a week. Eventually, they start spending a lot of time together and even kiss. When Frank suggests that they touch more, Helen tells him that she cannot have sex with someone unless she is sure that she loves him. Frank tries to control his urges.
Morris Bober enjoys working with Frank and the two men tell stories to each other during the day. One day, Morris starts to suspect Frank of stealing because revenues do not equal what Morris thinks that they should be. He starts watching Frank closely. Frank, at the same time, is overcome by his guilty conscience and decides to repay all the money he has stolen. He places six dollars back in the register one day, but when he realizes that he will need some money for that night, he steals a dollar back. Morris catches him and is heartbroken. Still, he orders Frank to leave.
The same night, Helen goes to meet Frank late in the park. She has decided that she loves him and will have sex with him. When she gets to the park, a drunk Ward Minogue, whom she knows from primary school, tries to rape her. Frank appears and rescues her, but proceeds to rape her himself.
The following day, Morris Bober falls asleep in his apartment with the radiator unlit, flooding his rooms with gas and almost killing himself. Frank and Nick Fuso save him. Morris contracts pneumonia and has to go to the hospital. Frank keeps the store open for the weeks when Morris is sick. Business is terrible because two Norwegians have just reopened the competing grocery and all the customers have gone there. Frank gives all of his personal savings to the grocery and works all night long at a different job to keep it afloat. Still, when Morris returns to the shop he makes Frank leave. Morris himself then tries to save the business by finding another job, but he cannot. A mysterious man appears one night offering to burn the store down so that Morris can collect the insurance money, but Morris turns him down. Later Morris tries to light such a fire himself, but nearly burns himself to death before Frank appears and rescues him. Morris again orders Frank out.
One night, Ward Minogue, who has been diagnosed with diabetes and who is acting desperately, sneaks into the Karp's liquor store through a broken back window. After getting drunk, Ward accidentally sets the store on fire. Karp's store and building are ruined. The next day, Karp, who has insurance, offers to buy Morris's store and grocery so that he can reopen. Morris feels happy and goes out to shovel snow for the pedestrians, although he fails to wear his coat. Later that night, he falls sick and dies three days later from pneumonia.
After Morris's death, Frank Alpine starts running the store. He works all night at a different job and tries everything to make the store work, but times are tough. Still, he decides that he wants to pay for Helen to attend college. At the end of the book, Helen has become friendlier to Frank and seems ready to accept his offer of tuition. Frank himself has changed utterly becoming completely honest and very much like Morris Bober, whose store and philosophies he now embraces. In his final act, Frank Alpine goes to the hospital, has himself circumcised and after Passover becomes a Jew.