Okay, first, a few ground rules for this summary. One Hundred Years of Solitude jumps back and forth in time so much it makes our heads spin. So to make things simpler, we're going to summarize the events in linear time, not the order in which they appear in the novel. Basically, be sure you've read it cover to cover already, just so we don't spoil anything for you.
Here goes. José Arcadio Buendía and his cousin, Úrsula, fall in love and decide to get married without their families' permission. Úrsula is stressed that incest isn't best and that it will lead to a child with a pig's tail, so she doesn't want to consummate the marriage. José Arcadio Buendía wins a cockfight, and the loser, Prudencio Aguilar, teases him about his wife not putting out. He gets mad, kills Prudencio, then goes home and has sex with his wife. Prudencio Aguilar's ghost starts to haunt José Arcadio and Úrsula until they decide to pack up and go found a new city, Macondo, with some of their friends. Their idea is to set up the town near the sea, but they can't find it and eventually give up looking.
José Arcadio Buendía and Úrsula have two sons, José Arcadio (II) and Aureliano. Like all the future José Arcadios, this one is strong and tough, and like all the future Aurelianos, this one is nerdy, bookish, and clairvoyant. The town mainly gets its view of the outside world from a group of nomadic gypsies, headed by Melquíades, who brings real-life and magical inventions to Macondo – things like ice, flying carpets, magnifying glasses, and magnets. José Arcadio Buendía usually wants to turn every new thing into a weapon.
Tired of being so isolated from modern developments, José Arcadio leads a band of dudes on a mission to try to find a route to the sea and thus get contact with the outside world. They get stuck in the jungle, go kind of crazy, and eventually give up. Meanwhile, back home, José Arcadio (II) has sex with Pilar Ternera, knocks her up, freaks out at impending fatherhood, falls in love with a little gypsy girl, and runs off with the caravan. Trying to find him, Úrsula leaves Macondo and comes back a few months later having found a route to another town, connecting Macondo to the world. New people start coming to the town, and the government sends over a mayor-type guy, Don Apolinar Moscote.
Pilar Ternera gives her baby to the Buendía family, and he is named Arcadio and raised without knowing who his 'rents are. Also joining the family are Rebeca, an orphan who arrives with a letter for José Arcadio and a bag of her parents' bones, and Amaranta, a new baby born to Úrsula and José Arcadio. Aureliano falls in love with Don Apolinar's beautiful nine-year-old child, Remedios.
Suddenly, the town is hit by a plague. The main symptoms are insomnia and complete memory loss. José Arcadio and Aureliano try to fight the disease first by posting signs labeling everything, and then by creating a memory machine. But it's no use. In the nick of time, they are rescued by Melquíades, who has a potion to bring all the memories back. Melquíades claims that he's back from the dead, and he holes up in a room in the house to write manuscripts in a secret code and teach Aureliano how to be a goldsmith.
Another memory that pops up after the plague is the ghost of Prudencio Aguilar, who has spent years trying to find José Arcadio and Macondo. He hangs out with José Arcadio for a long night, and the next day José Arcadio has gone completely insane. The family ties him to a tree in the backyard where he seems happy, speaking some language no one can understand.
Meanwhile, Aureliano is tortured by his feelings for little girl Remedios and goes to bed with Pilar Ternera to make himself feel better. It doesn't work, and he ends up getting her pregnant in the process. But she does agree to set up the marriage. After Remedios finally gets her period, she and Aureliano marry and he is extremely happy for the first time in his life.
Úrsula decides to liven up the house and throw a party. Part of the prep is buying a player-piano, which comes with a technician named Pietro Crespi. Both Rebeca and Amaranta fall in love with him, and a bitter hatred and rivalry starts up between them. Pietro prefers Rebeca and they become engaged, while Amaranta plots ways to disrupt the wedding. Finally, the wedding is about to happen, and Amaranta decides to murder Rebeca. But she prays hard for some other thing to happen so she doesn't have to go through with it. The other thing that happens? Remedios dies from some kind of pregnancy complication.
José Arcadio (II) suddenly comes back, giant, tattooed, and wild. He's been a sailor. When he gets home, he and Rebeca have instant chemistry and get married despite the fact that everyone is grossed out by the almost-incest. Pietro Crespi now falls in love with Amaranta, but she rejects him and he ends up killing himself.
After Remedios' death, Aureliano starts to become more and more political. At first he's on the side of his father-in-law, the Conservative town mayor Don Apolinar, but when he sees how super-corrupt the Conservative government is, he decides to join up with the Liberals. They turn out to be better, so Aureliano starts calling himself Colonel Aureliano Buendía and becomes a leader in a civil war between the Liberals and the Conservatives. The Colonel loses all of the rebellions he starts all over the country, but manages to constantly escape death in a series of close calls and assassination attempts. Also, while he travels, a lot of beautiful women come to his tent at night to sleep with him – it's apparently a thing, like back in the days of gladiators. He ends up fathering seventeen sons, all named Aureliano. Eventually he is captured and put in front of a firing squad, but his brother José Arcadio (II) rescues him.
The civil wars are endless and relentless. Back home, Arcadio, the secret son of José Arcadio (II), marries Santa Sofía de la Piedad. While she is pregnant Arcadio is put in charge of Macondo by Colonel Aureliano Buendía. He turns out to be a horrible tyrant, making up for the all the sad indignities of his childhood, and is finally executed by firing squad. He and Sofía have three kids: Remedios, and the twins Aureliano Segundo and José Arcadio Segundo.
When the civil war finally ends, Colonel Aureliano Buendía is forced to sign a demoralizing peace agreement, and his depression and loner-ism become extreme. He comes home and spends the rest of his life making tiny gold fishes, melting them down, and making them again.
But hey, life goes on – this time in the form of Americans and a banana plantation. At first, the company and its doings are hunky-dory, but eventually the workers get upset about their terrible working conditions and they strike. The company pretends to hold a meeting to come to terms, but instead it gathers the 3,000 workers together in a square and slaughters them with machine guns.
José Arcadio Segundo, who was a foreman at the plantation and is one of the key strike leaders, is one of the only survivors. When he comes to after the massacre, he is on a train of corpses on their way to be dumped into the sea. He just barely escapes, and when he gets back to Macondo, no one knows the massacre has happened. For the whole rest of the novel, all the people in the town stick to the government line that the strike ended peacefully and all the workers just went home. The banana company leaves and the plantation shuts down.
While all that was going on, Aureliano Segundo fell in love with Petra Cotes, but goes off and marries a super-strict, super-religious, kind-of-crazy woman named Fernanda. After the wedding, he goes back and forth between them. While he's with Petra Cotes, their farm animals breed crazily and he becomes extremely wealthy. With Fernanda he has a daughter, Meme, and a son, José Arcadio (III).
Meme falls in love with a mechanic named Mauricio Babilonia. Fernanda discovers them, has Mauricio shot as a thief, and ships Meme off to a convent. A year later, a nun comes to Macondo with Aureliano (II), Meme's baby, who becomes a huge persona non grata (unwelcome person) at the house, and who is raised in near-captivity playing alongside Fernanda and Aureliano Segundo's last daughter, Amaranta Úrsula, without knowing that he's related to the Buendías.
Then it starts to rain. It rains for almost five years straight without interruption. Most of the town is completely destroyed, rotted, and washed away. Úrsula, the last of the original Buendías, dies. Everyone who is still alive starts dying off. Amaranta Úrsula goes off to Belgium, and eventually Aureliano (II) is left alone in the house. José Arcadio (III) comes back, starts an orgy lifestyle with some local kids, and they eventually kill him for his money. Then Amaranta Úrsula comes back with her husband, a Flemish pilot. After a while, she and Aureliano (II) end up getting it on, and the husband leaves. As their love grows, the house and the town fall more and more into complete nothingness.
Amaranta Úrsula becomes pregnant, and neither she nor Aureliano (II) knows that they are actually aunt and nephew. She dies during childbirth, after giving birth to a baby with the tail of a pig – just as Úrsula had been worried about all this time, bringing the story full circle. Totally depressed, Aureliano (II) goes and gets drunk. By the time he remembers the baby, little Aureliano (III) has been eaten by ants.
Aureliano (II) freaks out but can't do anything except go and finally translate the scrolls that Melquíades had left behind, which turn out to be the whole history of the Buendía family, from the patriarch tied to a tree to the baby devoured by ants. As he finishes reading the story, Aureliano (II), the house, and the rest of the town are wiped away by a hurricane. Everything is gone from memory, history, and existence.