The protagonist of the No Longer at Ease, Obi Okonkwo, is a young man born in Ibo in the Eastern Nigerian village of Umuofia. He was well educated and eventually sent to study law in England, a course of study he eventually changed to English. He stays in England for nearly four years, at times longing for the warm weather of home and all the other nostalgic qualities his memory supplies him during long winters abroad. Nevertheless, his arrival is less than what he has expected.

Because he is educated, he is given a "European post," and he works in an office whose ethics he finds repulsive. He stands firmly against the bribery that goes on and is opposed to his boss, a very old, white, and English colonial man named Mr. Green. Obi finds himself in a constant battle between traditions of the world into which he was born (that of the village and his traditional African roots), represented by the Umuofian Progressive Union, and the conventions of a changing world.

Obi finds himself at the beginning of a generation of change, caught between two worlds. He is unable to marry the woman that he loves because she is considered an outcast. He claims to want to marry her anyway because by the time he has children, the world will have changed, and it will not matter, just as it does not matter now that his father is a convert to Christianity (a conversion that was once quite scandalous). Still, Obi loses his fiancée, his mother, and finds himself in serious debt throughout the course of the novel. He must pay back his scholarship loan and is responsible for sending money home. Eventually, Obi breaks under all of this pressure and gives in to the bribery he had stood against so idealistically, but he does not give in without guilt. At the end, he even claims to be finished with bribery, right before he is caught. Somehow it is too late, and his situation, his position of being caught between two shifting worlds, becomes almost impossible.

Obi's birth name is Obiajulu which means "the mind at last is at rest," and this naming is a looming irony, considering the title of the novel and Obi's predicament. Obi is ill at ease in both of his cultural experiences—he lies in the middle, a difficult place.