Located near Washington Square Park in the Asch building, which had been constructed just 10 years prior, the Triangle Shirtwaist Company employed mostly young immigrant women to sew "shirtwaists", which were fancy blouses resembling mens dress shirts. Working in sweatshop-like conditions, the factory workers could not escape when a fire began in a bin of fabric scraps on the 8th floor. The building had insufficient safety infrastructure, with no sprinklers and inadequate fire escapes and elevators for the factory's hundreds of workers. Most disturbingly, the doors to the stairwells could only be opened from the outside and swung inward, which sealed the workers inside. As the fire spread, some were forced to jump from the building or down the elevator shaft to escape the flames. Others fell while attempting to escape down a flimsy rear fire escape that had only been installed to meet the minimum requirements of the city's burgeoning fire code. The fire would stand as the city's deadliest single-day event until the September 11th attacks.

In the wake of the fire, the city improved fire safety requirements, introducing common features we take for granted today, such as exit signs, doors that swing outwards in commercial buildings, and improvements to firefighting equipment that can sufficiently pump large amounts of water up to the highest floors of New York's buildings. Today, the site of the fire is known as the Brown Building, and is part of the NYU campus.