On September 22, 1993, an Amtrak Sunset Limited passenger train derailed on the CSX Transportation Big Bayou Canot Bridge near Mobile, Alabama, United States. It was caused by displacement of a span and deformation of the rails when a tow of heavy barges collided with the rail bridge eight minutes earlier. Forty-seven people were killed and 103 more were injured. To date, it is the deadliest train wreck in both Amtrak's history and Alabama's railway history. It is also the worst rail disaster in the United States since the 1958 Newark Bay rail accident, in which 48 people died.

Prior to the derailment, a barge pushed by the towboat Mauvilla (owned and operated by Warrior and Gulf Navigation of Chickasaw, Alabama) made a wrong turn on the Mobile River and entered the Big Bayou Canot, a channel of water closed to commercial boat traffic and crossed by a CSX Transportation rail bridge.

The towboat's pilot, Willie Odom, was not properly trained on how to read his radar and so, due to very poor visibility in heavy fog and his lack of experience, did not realize he was off course. The boat also lacked a compass and a chart of the waters. Odom believed that he was still on the Mobile River and had identified the bridge in the radar as another tug boat. After the investigation, he was found not to be criminally liable for the incident.

The bridge was struck by the Mauvilla at about 2:45 a.m. The span had been designed to rotate so it could be converted to a swing bridge by adding appropriate equipment. No such conversion had been performed but the span had not been adequately secured against unintended movement. The collision forced the unsecured end of the bridge span approximately 3 feet (1 m) out of alignment and severely kinked the track.

Despite the displacement of the bridge, the continuously welded rails did not break. As a result, the track circuit controlling the bridge approach block signals remained closed (intact) and the nearest signal continued to display a clear (green) aspect. Had one of the rails been severed by the bridge's displacement, the track circuit would have opened, causing the approach signal to display a stop (red) aspect and the preceding signal a yellow (caution) approach indication. This might have given the Amtrak engineers sufficient time to stop the train or at least reduce its speed in an effort to mitigate the accident's severity.

At 2:53 a.m., Amtrak's Sunset Limited train, powered by three locomotives (one GE Genesis P40DC number 819 in the front and two EMD F40PHs, numbers 262 and 312) en route from Los Angeles, California, to Miami, Florida, with 220 passengers and crew aboard, crossed the bridge at around 70 miles per hour (110 km/h) and derailed at the kink. The first of its three locomotives slammed into the displaced span, causing that part of the bridge to collapse into the water beneath. The lead locomotive embedded itself nose-first into the canal bank and the other two locomotives, together with the baggage car, sleeping car and two of the six passenger cars, plunged into the water. The locomotives' fuel tanks, each of which held several thousand gallons of diesel fuel, ruptured upon impact, resulting in a massive fuel spill and a fire. Forty-seven people, including the train’s three engineers, two crew members, and 42 passengers were killed – many by drowning, others by fire/smoke inhalation. Another 103 were injured. The towboat's four crew members were not injured. Odom helped save 17 people after the crash using the same towboat that had been pushing the barge that hit the bridge.

The National Geographic documentary program Seconds From Disaster also examined the derailment. In addition to corroborating findings of the official accident report, the program revealed that the train had been delayed in New Orleans by repairs to an air conditioner unit and a toilet. This had put it a half-hour behind schedule. If not for this delay, the Sunset Limited would have passed over the Big Bayou Canot bridge 20 minutes before the bridge was hit by the barge.

As a result of its investigation of this derailment, the National Transportation Safety Board (NTSB) made a comprehensive series of recommendations, on September 19, 1994, to the U.S. Department of Transportation, the U.S. Army Corps of Engineers, the U.S. Coast Guard, the Federal Emergency Management Agency, Amtrak, the American Waterways Operators, Inc., the Warrior & Gulf Navigation Company, the Association of American Railroads, and the American Short Line Railroad Association. Following a recommendation to maintain a record of onboard passenger numbers, Amtrak now records passenger lists electronically.

• Andrea Chancey — 11-year-old wheelchair-using "miracle child" with cerebral palsy, whose parents died in the crash
• Ken Ivory and Michael Dopheide — honored by the Coast Guard for saving lives after the crash
• R. C. Sproul — related his experience in the crash

• List of bridge failures

• Holloway, David Mobile Press-Register 200th Anniversary: Sunset Limited train wreck memories not diminished by passing years at al.com, 1 July 2013. Retrieved 3 June 2014
• Sproul, R. C. Train Wreck Eyewitness account of aftermath, at Ligonier Ministries blog. Retrieved 3 June 2014
• Summary and photos at Trainweb.org. Retrieved 3 June 2014
• Graphical re-enactment of accident cause at TMBA Inc Animation Studio, New York. Retrieved 3 June 2014
• U.S. Coast Guard: The short film Aerial and Boat Views of Amtrak Train Derailment, Mobile, Alabama (1993) is available for free viewing and download at the Internet Archive.