William Mandella is a physics student conscripted for an elite task force in the United Nations Exploratory Force being assembled for a war against the Taurans, an alien species discovered when they apparently suddenly attacked human colonists' ships. The UNEF ground troops are sent out for reconnaissance and revenge.
The elite recruits have IQs of 150 and above, are highly educated, healthy, and fit. Training is gruelling– first on Earth, in Missouri, and later on a planet called "Charon" beyond Pluto (written before the discovery of the actual planetoid). Several of the recruits are killed during training, due to the extreme environments and the use of live weapons. The new soldiers then depart for action, traveling via interconnected 'collapsars' that allow ships to cover thousands of light-years in a split second. However, traveling to and from the collapsars at near-lightspeed has massive relativistic effects.
Their first encounter with Taurans on a planet orbiting Epsilon Aurigae turns into a post-hypnotically suggested massacre, with the unresisting enemy wiped out. This first expedition, beginning in 1997, lasts only two years for the soldiers, but due to time dilation, decades have passed on Earth. On the long way home, the soldiers experience future shock first-hand, as the Taurans employ increasingly advanced weaponry against them while they do not have the chance to re-arm.
Mandella, with soldier, lover, and companion Marygay Potter, returns to civilian life, only to find humanity drastically changed. He and his fellow soldiers have difficulty fitting into a society that has evolved almost beyond their comprehension. The veterans learn that, to curb overpopulation, which led to worldwide class wars caused by inequitable rationing, homosexuality has become officially encouraged by many of the world's nations. The world has become a very dangerous place due to widespread unemployment and the easy availability of deadly weapons. The changes within society alienate Mandella and the other veterans to the point where many re-enlist to escape, even though they realize the military is a soulless construct. Mandella attempts to get an assignment as an instructor on Luna, but is promptly reassigned by standing order to combat command. The inability of the military to treat its soldiers as more than highly complex valuable machines is a theme of the story.
Almost entirely through luck, Mandella survives four years of military service, while several centuries elapse elsewhere. He soon becomes the objectively oldest surviving soldier in the war, attaining high rank through seniority, not ambition (he is essentially a pacifist who acts mostly from talent and a melancholic sense of duty). He and Marygay (who has remained his last contact with the Earth of his youth) are finally given different assignments, meaning it will be extremely unlikely they will ever see each other again (assuming they both survive). As the commanding officer of a 'strike force', Mandella commands soldiers who speak a language largely unrecognizable to him, whose ethnicity is now nearly uniform and who are exclusively homosexual. He is disliked by his soldiers because they have to learn 21st century English to communicate with him and other senior staff, and because he is heterosexual.
Engaging in combat thousands of light years away from Earth, Mandella and his soldiers need to resort to medieval weapons in order to fight inside a stasis field which neutralizes all electromagnetic radiation in anything not covered with a protective coating. It turns out to be the last conflict of the war. Humanity has begun to clone itself, resulting in a new, collective species calling itself simply Man . Man is able to communicate with the Taurans, who are also clones. It is discovered that the war started due to a misunderstanding. The futile, meaningless war that lasted for more than a thousand years ends.
Man has established several colonies of old-style, heterosexual humans, just in case the evolutionary change proves to be a mistake. Mandella travels to one of these colonies, named "Middle Finger" in the definitive version of the novel. There, he is reunited with Marygay, who had been discharged much earlier and had taken trips in space to use time dilation to age at a much slower rate, hoping and waiting for Mandella's return. The epilogue is a news item from the year 3143 announcing the birth of a "fine baby boy" to Marygay Potter-Mandella.