The Triangle Waist Company, owned by Max Blanck and Isaac Harris, produced women's blouses known as shirtwaists. The factory employed about 500 workers, mostly young immigrant women and girls who worked nine hours a day on weekdays and seven on Saturdays, earning between seven and twelve dollars for their fifty-two-hour week. The owners preferred hiring immigrant women because they would accept lower wages and were less likely to organize. Many of these workers were poor, young, with little education and limited English. The factory occupied the 8th, 9th, and 10th floors of the ten-story Asch Building, which had been built in 1901. The stairwell doors were locked during working hours, a common practice that owners justified as preventing unauthorized breaks and reducing theft. Others have noted it also kept out union organizers. Hundreds of pounds of fabric scraps piled in wooden bins beneath the cutting tables, surrounded by hanging fabrics. The steel trim was the only material in the room that would not burn.

The fire started in a scrap bin under a cutter's table on the eighth floor. Within three minutes, the Greene Street stairway was unusable in both directions. The foreman who held the key to the locked stairway door had already escaped by another route. Workers on the eighth floor who knew the building had a chance: some reached the roof via the Greene Street stairs before the fire blocked them, others crammed into the elevators while they still operated. The ninth floor was a death trap. Workers there had no warning and found their exits sealed. Some tried to use the single fire escape, which buckled and collapsed under the weight of fleeing bodies. Others crowded the windows. Onlookers on Washington Place watched as workers, their clothing already aflame, stepped onto the ledge and fell. The fire department arrived quickly, but their ladders reached only to the sixth floor. The safety nets tore under the impact. The entire catastrophe, from the first flame to the last body, unfolded in roughly eighteen minutes.

Blanck and Harris survived by fleeing to the roof. They were indicted on first- and second-degree manslaughter charges. At trial, their attorney Max Steuer systematically undermined survivor testimony by having witnesses repeat their accounts until the jury suspected coached statements. The prosecution argued the owners knew the exit doors were locked. The jury acquitted both men. A subsequent civil suit in 1913 found them liable for wrongful death, awarding plaintiffs seventy-five dollars per victim. Their insurance company, meanwhile, paid Blanck and Harris $64,925 more than their reported losses, roughly $445 per casualty. In 1913, Blanck was arrested again for locking factory doors during working hours. He was fined twenty dollars. The two partners eventually closed the Triangle Waist Company in 1918.

The fire galvanized reform with a speed that the labor movement had struggled to achieve for decades. Frances Perkins, who witnessed the disaster from the street, formed a Committee on Public Safety and began lobbying for new legislation. She would go on to become the first female United States Secretary of Labor. In Albany, Tammany Hall's Al Smith and Robert F. Wagner championed an investigative commission that interviewed 222 witnesses, collected 3,500 pages of testimony, and dispatched field agents to inspect factories across the state. Fire Chief John Kenlon told investigators his department had identified more than 200 factories where conditions made a Triangle-style disaster possible. The commission's findings produced thirty-six new laws in New York State mandating better building access and egress, fireproofing, fire extinguishers, alarm systems, automatic sprinklers, and limits on working hours for women and children. By 1913, sixty of sixty-four recommended reforms had been enacted. Rose Schneiderman, the union activist, captured the mood at a memorial meeting in the Metropolitan Opera House: the time for patience was over.

The Asch Building still stands at 23-29 Washington Place, now called the Brown Building and part of the New York University campus. It is both a National Historic Landmark and a New York City landmark. For years, the only formal commemoration was a set of plaques on the building's corner. But a public art project called Chalk, started in 2004 by filmmaker Ruth Sergel, began an annual tradition of inscribing the names, ages, and causes of death of each victim in chalk on the sidewalks outside their former homes across New York City. In 2023, more than a century after the fire, a permanent memorial was unveiled on the building itself: a steel ribbon descends from the upper floors, then splits into two horizontal ribbons twelve feet above street level, listing the names and ages of all 146 victims as holes cut through the steel. The last living survivor, Rose Freedman, had died in 2001 at the age of 107. She had been two days short of her eighteenth birthday when she followed the company executives to the roof and was rescued. She spent the rest of her long life as a union supporter.