The Left Hand of Darkness is the story of Genly Ai, ambassador of an intergalactic confederacy known as the Ekumen, and his journey to the planet Winter. The human inhabitants of Winter are ambisexual, spending most of their time in an androgynous state and adopting male or female sexual characteristics during a monthly mating period. Genly's story explores Western conceptions of sex and gender, as well as the idea of androgyny.
The protagonist of the novel is Genly Ai, a male Terran native, who is sent to invite Gethen to join the Ekumen, the coalition of humanoid worlds. Ai travels to the Gethen system on a ship which remains in solar orbit with Ai's companions, who are in stasis; Ai himself is sent to Gethen alone, as the "first mobile." Like all envoys of the Ekumen, he can "mindspeak"—a form of quasi-telepathic speech, which Gethenians are capable of, but for which they have lost the ability. He lands in the Gethenian kingdom of Karhide, and spends two years attempting to persuade the members of its government of the value of joining the Ekumen. Karhide is one of two major nations on Gethen, the other being Orgoreyn.
The novel begins the day before an audience that Ai has obtained with Argaven Harge, the king of Karhide. Ai manages this through the help of Estraven, the prime minister, who seems to believe in Ai's mission, but the night before the audience, Estraven tells Ai that he can no longer support Ai's cause with the king. Ai begins to doubt Estraven's loyalty because of his strange mannerisms, which Ai finds effeminate and ambiguous. The behavior of people in Karhide is dictated by shifgrethor , an intricate set of unspoken social rules and formal courtesy. Ai does not understand this system, thus making it difficult for him to understand Estraven's motives, and contributing to his distrust of Estraven. The next day, as he prepares to meet the King, Ai learns that Estraven has been accused of treason, and exiled from the country. The pretext for Estraven's exile was his handling of a border dispute with the neighboring country of Orgoreyn, in which Estraven was seen as being too conciliatory. Ai meets with the king, who rejects his offer to join the Ekumen. Discouraged, Ai decides to travel through Karhide, as the spring has just begun, rendering the interior of the country accessible.
Ai travels to a fastness, a dwelling of people of the Handarrata, one of two major Gethenian religions. He pays the fastness for a foretelling, an art practiced to prove the "perfect uselessness of knowing the answer to the wrong question." Ai decides to pursue his mission in Orgoreyn. He asks if Gethen/Winter will be a member of the Ekumen in five years, expecting that the foretellers will give him an ambiguous response; however, he is answered "yes". This leads him to muse that the Gethenians have "trained hunch to run in harness." After several months of travelling through Karhide, Ai decides to pursue his mission in Orgoreyn, to which he has received an invitation.
Ai reaches the Orgota capital of Mishnory, where he finds that the Orgota politicians are initially far more direct with him. He is given comfortable quarters, and is allowed to present his invitation to the council that rules Orgoreyn. Three members of the council, Shusgis, Obsle, and Yegey, are particularly supportive of him. These three are members of an "Open Trade" faction, which wants to end the conflict with Karhide. Estraven, who was banished from Karhide, is found working with these council members, and tells Ai that he was responsible for Ai's invitation to Orgoreyn. Despite the support, Ai feels uneasy; Estraven warns him not to trust the Orgota leaders, and he hears rumors of the "Sarf," or secret police, that truly control Orgoreyn. He ignores both his feeling and the warning, and is once again blindsided; he is arrested unexpectedly one night, interrogated, and sent to a far-northern work camp where he suffers harsh cold, is forced into hard labor, and is given debilitating drugs intended to prevent kemmer.
His captors expect him to die in the camp, but to Ai's great surprise, Estraven—whom Ai still distrusts—goes to great lengths to save him. Estraven poses as a prison guard and breaks Ai out of the farm, using his training with the Handarrata to induce dothe , or berserker strength to aid him in the process. Estraven spends the last of his money on supplies, and then steals more, breaking his own moral code which would forbid stealing. The pair begin an 80-day trek across the Gobrin ice sheet back to Karhide, because Estraven believes that the very appearance of Ai in Karhide will force its acceptance of the Ekumen treaty. Over the journey Ai and Estraven learn to trust and accept one another's differences. Ai is eventually successful in teaching Estraven mindspeech; Estraven hears Ai speaking in his mind with the voice of his dead sibling Arek, demonstrating the close connection that the two have developed. When they reach Karhide, Estraven tries to return to the land border with Orgoreyn, because he is still exiled from Karhide, but is killed by border guards, who capture Ai. Estraven's prediction is borne out when Ai's presence in Karhide, along with the fallout from Estraven's death, triggers the collapse of governments in both Karhide and Orgoreyn. Soon after, Karhide agrees to join the Ekumen, followed shortly by Orgoreyn, completing Ai's mission.