Jurgis Rudkus and Ona Lukoszaite are two young newlyweds who have recently emigrated from Lithuania to make their livelihood in Chicago. They have settled in the city's "Packingtown" area, where a largely immigrant population lives in squalor and works grueling jobs to survive. The couple celebrates their marriage at a local bar, and many guests leave without contributing money to defray the cost of the party, as is customary in Lithuania. This leaves the couple in debt, which distresses the family.
Jurgis finds work at a local slaughterhouse and Ona's cousin Marija gets a job in a cannery. Jurgis's father, Dede Antanas, also looks for a job, but is too old to be employable. The family naively decides to buy a home but is tricked into signing an exploitative lease instead; their financial obligations build. Dede Antanas finds work only by agreeing to forfeit a third of his wages as a finder's fee. This corruption and "graft" is routine in Packingtown. Dede Antanas is worn down by his job and soon dies.
An unforgiving winter arrives. Marija's factory closes and she cannot to marry her love, Tamoszious Kuszeika. Jurgis tries to learn English, and as he tries to assimilate he begins to learn about the political corruption and vote-buying that dominate Chicago's government. In the springtime, Marija is rehired at the cannery. However, she is fired for standing up for herself when a higher-up tries to swindle her out of wages. Ona, now pregnant, has taken a meatpacking job under a hostile overseer named Miss Henderson. Ona gives birth to a boy, whom she and Jurgis name Antanas; she is forced back on the job after just one week's rest.
Jurgis sprains his ankle on the job and is incapacitated for three months. Instead of compensating him, Jurgis's employers simply cut off his pay and replace him. The family's unity frays: when a snowstorm confines them indoors, Jurgis beats Ona's stepmother Elzbieta's son Stanislovas for being unable to go to work. Jonas, Elzbieta's brother, abandons the family. Elzbieta's crippled son Kristoforas dies.
Jurgis recovers from his injury, but his factory will not rehire him. His only option is working in the fertilizer plant, the most miserable workplace in town. He begins to reek of the noxious chemicals he handles. To cope, Jurgis turns to alcohol. Meanwhile, Ona—pregnant again—does not return from work and begins to lie about her whereabouts. Jurgis uncovers that Ona's supervisor, Phil Connor, has been manipulating her for sex. Jurgis attacks Connor and is imprisoned. In jail, Jurgis befriends a savvy safecracker named Jack Duane.
Released from jail, Jurgis learns that his family has been evicted. Jurgis finds them in a boardinghouse, and discovers Ona in premature labor. She dies an excruciating death. Jurgis, devastated, goes on a drinking binge. Afterwards, Jurgis secures work making harvesting equipment. The family's fortunes seem to have improved, but Jurgis suddenly loses his job, and baby Antanas, his only joy in life, drowns in a flooded street. Jurgis runs away to live as a vagrant in the countryside.
Jurgis returns to Chicago. He works digging tunnels and spends freely, confident he'll have money to weather the winter. However, he is hurt on the job and emerges from the hospital destitute. Reduced to begging, he is given a hundred dollar bill by the son of a packing magnate, but a bartender swindles him out of the cash. Furious, Jurgis tries to fight, but nobody believes his story and he is sent back to jail.
In jail, Jurgis reencounters Jack Duane, who convinces him to get involved with Chicago's criminal underworld. Jurgis starts with small-time muggings, but soon grows more and more unscrupulous—he begins lucrative work as a crony of a corrupt Democratic Party boss named Mike Scully. When a strike breaks out, he crosses the union by working as a scab. Jurgis benefits from graft until he encounters Phil Connor and attacks him a second time. Connor turns out to be Scully's friend, and Jurgis must spend all his savings to avoid prosecution.
Destitute again, Jurgis reunites with Marija, now a cynical, morphine-addicted prostitute. Jurgis is at the end of his rope when he chances upon a socialist rally. The movement's message of unified workers and democratically-owned industry inspires Jurgis. He becomes a tireless advocate for socialism and gets a job as a porter in a socialist-run hotel. The book ends with an encouraging, pro-socialist message: the socialist party has made great gains in recent elections, and a socialist orator proclaims that with continued activism, "Chicago will be ours!"