| Fatalities | Year | Article | Type | Location | Damage (US$) | Comments |
| 6,000–12,000 | 1900 | 1900 Galveston hurricane | Tropical cyclone | Texas | $34,000,000 (1900) | |
| 5,000 | 1936 | 1936 North American heat wave | Heat wave | United States, Canada | | |
| 4,000+ | 1862 | Great Flood of 1862 | Flood | Western United States | $100,000,000(1862) | |
| 3,389 | 1899 | 1899 San Ciriaco hurricane | Tropical cyclone | Puerto Rico, East Coast of the United States | $20,000,000(1899) | |
| 3,000+ | 1906 | 1906 San Francisco earthquake | Earthquake and fire (urban conflagration) | San Francisco, California | $235,000,000(1906) | Conflagration followed quake; fatalities estimated; also major casualties in Santa Rosa and San Jose. Deadliest earthquake in U.S. history. |
| 2,996 (2,977 ex. perps) | 2001 | September 11 attacks | Terrorism | New York City, Arlington County, Virginia, and Stonycreek Township near Shanksville, Pennsylvania | $10,000,000,000(2001) | 2,977 victims and 19 hijackers. Deadliest disaster in New York City and the Washington, D.C. metropolitan area. Deadliest act of terrorism in world history. |
| 2,982 (estimated) | 2017 | Hurricane Maria | Tropical cyclone | Puerto Rico, United States Virgin Islands, East Coast of the United States | $94,500,000,000(2017) | Total includes at least 2,975 deaths based on a study by GWU on the estimated excess mortality. The official death count was previously 64. The storm caused $90 billion (2017 USD) in damage in Puerto Rico, and three deaths in the U.S. Virgin Islands, plus 75 deaths and $1.6 billion in damage across the rest of the Caribbean. |
| 2,823 | 1928 | 1928 Okeechobee hurricane | Tropical cyclone | Florida, Puerto Rico | $800,000,000(2005) | 4,000+ believed dead total. Includes 2,511+ in the contiguous United States, 312 in Puerto Rico. |
| 2,467 | 1941 | Attack on Pearl Harbor | Military strike – bombing | Honolulu, Territory of Hawaii and nearby military installations | | victims and 64 Japanese attackers. Deadliest attack on U.S. soil by a foreign government. |
| 2,209 | 1889 | Johnstown Flood | Accident – dam failure | Pennsylvania | | Much rain, deforestation; dam failed |
| 2,000 | 1893 | 1893 Cheniere Caminada hurricane | Tropical cyclone | Louisiana | | Fatalities estimated |
| 1,700 | 1980 | 1980 United States heat wave | Heat wave | Central and southern states | $20,000,000,000(1980 USD) | Official death toll, may have been higher |
| 1,547-1,864 | 1865 | Sultana | Accident – shipwreck | Marion, Arkansas | | Steamboat sank due to boiler explosion; fatalities estimated. Deadliest maritime disaster in U.S. history |
| 1,500–2,500 | 1871 | Peshtigo Fire | Wildfire | Peshtigo, Wisconsin, Upper Peninsula of Michigan | | Fatalities estimated; most deaths in one fire in U.S. history |
| 1,500 | 1896 | 1896 Eastern North America heat wave | Heat wave | Northeastern United States, Midwestern United States | | Fatalities estimated |
| 1,392 | 2005 | Hurricane Katrina | Tropical cyclone | Florida, Louisiana, Mississippi, Alabama, Georgia, Kentucky, and Ohio | $125,000,000,000 (2005) | Tied with Hurricane Harvey as the costliest natural disaster in U.S. history. |
| 1,173 | 1943 | HMT Rohna | Military strike – bombing | Mediterranean Sea | | Luftwaffe glide bomb hit troopship causing the largest loss of U.S. soldiers (1,050) at sea due to enemy action in a single incident. |
| 1,021 | 1904 | PS General Slocum | Accident – shipwreck | East River near New York City | | Steamship sank due to fire on board. Deadliest maritime disaster in New York City, and deadliest in city's history until 2001. |
| 1,000–2,000 | 1893 | 1893 Sea Islands hurricane | Tropical cyclone | Georgia, South Carolina | | Fatalities estimated |
| 1,000 | 1918 | 1918 Cloquet fire | Wildfire (rural) | Minnesota | $7,300,000 | |
| 918 | 1978 | Jonestown | Mass murder | Jonestown, Guyana | | Jim Jones, cult leader of the Peoples Temple Agricultural Project, convinced most of the group to drink grape Flavor Aid poisoned with cyanide or to inject themselves and their children with cyanide, totaling 909 deaths of U.S. nationals. A family of four other Temple members committed murder/suicide by knife in Georgetown. Five others were shot and killed while trying to escape from Jonestown, including U.S. Congressman Leo Ryan. |
| 879 | 1945 | USS Indianapolis | Military strike – submarine | Philippine Sea | | Largest loss of life in the history of the U.S. Navy at sea |
| 844 | 1915 | SS Eastland | Accident – shipwreck | Chicago, Illinois | | Passenger ship capsized in Chicago harbor while loading charter for company picnic, causing great loss of life despite shallow water and proximity to land. Deadliest disaster in the history of Great Lakes shipping, and deadliest disaster in Chicago history. |
| 819 | 1944 | SS Léopoldville | Military strike – submarine | English Channel | | Approximately 763 United States Army soldiers drowned. |
| 800 | 1875 | 1875 Indianola hurricane | Tropical cyclone | Louisiana, Texas | | Fatalities estimated |
| 749 | 1944 | Exercise Tiger | Military strike – E-boats | English Channel | | USS LST-289, LST-507 and LST-531 sunk during a training exercise. |
| 747 | 1925 | Tornado outbreak of March 18, 1925 | Tornado outbreak | Missouri, Illinois, Indiana, Kentucky, Tennessee | $1,650,000,000(2005) | At least 12 tornadoes, including the following: 1925 tri-state tornado: 695 deaths (deadliest tornado in U.S. history) Buck Lodge, Tennessee/Beaumont, Kentucky: 41 deaths |
| 745 | 1919 | 1919 Florida Keys hurricane | Tropical cyclone | Florida, Texas | | Including 488 deaths aboard SS Valbanera |
| 739 | 1995 | Chicago Heat Wave of 1995 | Heat wave | Chicago, Illinois | | |
| 683 | 1942 | USS Juneau | Military strike – submarine | Guadalcanal | | Sunk by submarine while retreating with damage from naval battle of Guadalcanal. |
| 682–800 | 1938 | 1938 New England hurricane | Tropical cyclone | | | |
| 675 | 1943 | SS Dorchester | Military strike – submarine | Greenland | | United States troopship. |
| 650 | 1913 | Great Flood of 1913 | Flood | Central United States, Eastern United States | | Fatalities estimated |
| 644 | 1943 | USS Liscombe Bay | Military strike – submarine | Gilbert Islands | | Submarine torpedo detonated the aircraft carrier's bomb magazine during Operation Galvanic. |
| 602 | 1903 | Iroquois Theatre fire | Fire (building) | Chicago, Illinois | | Worst theater fire in American history; worst single-building fire. |
| 600 | 1928 | St. Francis Dam | Accident – dam failure | Santa Clarita, California | | |
| 581 | 1947 | Texas City disaster | Accident – explosion | Texas City, Texas | | Ammonium nitrate on board ship |
| 501+ | 1896 | Tornado outbreak sequence of May 1896 | Tornado outbreak sequence | Central United States, Southern United States | $2,900,000,000(1997) | At least 38 tornadoes, including the following: 1896 St. Louis–East St. Louis tornado: 255–400 deaths Sherman, Texas: 73+ deaths Ortonville–Thomas–Oakwood, Michigan: 47+ deaths Seneca–Oneida, Kansas/Falls City, Nebraska: 25+ deaths Imbs–Germantown, Illinois: 24 deaths |
| 500+ | 1804 | 1804 Antigua–Charleston hurricane | Tropical cyclone | Southeastern United States | | |
| 500 | 1865 | American steamship General Lyon (1864) | Accident – fire, shipwreck | Off Cape Hatteras, North Carolina | | Fatalities estimated |
| 500 | 1871 | Great Michigan Fire | Wildfire (rural) | Michigan | | Fatalities estimated |
| 492 | 1942 | Cocoanut Grove fire | Fire (building) | Boston, Massachusetts | | Deadliest nightclub fire ever, and second-deadliest structure fire in U.S. history; loss of life due to blocked exits; burn victims were among the first treated with penicillin |
| 476–1,000+ | 1927 | Hawks Nest Tunnel disaster | Industrial, silicosis | Gauley Bridge, West Virginia | | 178 admitted deaths, 476 with congressional inquiry, 1,000+ by epidemiologists. |
| 454+ | 1936 | 1936 Tupelo–Gainesville tornado outbreak | Tornado outbreak | Alabama, Arkansas, Mississippi, Georgia, South Carolina, Tennessee | | At least 12 tornadoes, including the following: Tupelo, Mississippi: 216+ deaths Gainesville, Georgia: 203+ deaths |
| 450–800 | 1862 | Dakota War of 1862 | Massacre | | | |
| 428 | 1913 | 1913 (Ohio) statewide flood | Flood | Ohio | | |
| 418+ | 1894 | Great Hinckley Fire | Wildfire (rural) | Hinckley, Minnesota and vicinity | | |
| 416 | 1957 | Hurricane Audrey | Tropical cyclone | Louisiana, Texas, Mississippi, Alabama | $147,000,000(1957) | |
| 408 | 1935 | 1935 Labor Day hurricane | Tropical cyclone | Florida | | |