Although the storm struck Galveston with 120-mph sustained winds, most of the deaths were caused by saltwater drowning, as a 16-foot storm surge washed over the city. This saltwater flood swept through the city, enabling large, destructive waves to pound many buildings and break them into pieces.

The Great Galveston Hurricane of September 8, 1900, remains the deadliest natural disaster in United States history, claiming an estimated 6,000 to 12,000 lives. The primary cause of death was the massive storm surge, which rose to nearly 15 feet (4.5 meters) above sea level. Because Galveston was a low-lying barrier island with its highest point only 8.7 feet above sea level, the surge completely inundated the city. The force of the water demolished more than 3,600 homes and buildings, turning the debris into a "wall of destruction" that acted like a giant saw, crushing everything and everyone in its path. Many victims who managed to survive the initial impact of the water succumbed to drowning as they were trapped under wreckage or swept out to sea. The lack of an adequate sea wall at the time and the late arrival of warnings meant that residents had little chance to evacuate or find high ground. In the aftermath, the city was raised by nearly 17 feet and a massive concrete sea wall was constructed to prevent a repeat of such a catastrophic loss of life from future storm surges.