A slow-moving trough moved eastward across the United States and interacted with a moist and unstable airmass originating from the Gulf of Mexico, resulting in widespread heavy rainfall, severe thunderstorms, and significant tornadoes over a four-day period.

A violent high-end EF4 tornado moved through the towns of Rolling Fork, Midnight, and Silver City in western Mississippi, causing catastrophic damage and many fatalities.

[8] On March 18, the Storm Prediction Center (SPC) first indicated the potential for organized severe weather across the Southern Plains in advance of an upper-level trough across the Western United States.

On March 22, the SPC issued a level 3/Enhanced risk of severe weather across portions of Louisiana, Arkansas, and Mississippi, for supercell thunderstorms capable of large hail, damaging winds, and strong (EF2+) tornadoes.

Meanwhile, a rapidly deepening low-pressure area was expected to drag a warm front northward, leading to a broad, unstable air mass to its south.

Initial forecaster thinking was that strong forcing for ascent across Arkansas would lead to an organized squall line capable of both tornadoes and damaging winds, whereas more discrete supercells would be possible farther south,[16] particularly along north–south oriented confluence bands in the open warm sector.

[17] A tornado watch was issued shortly thereafter at 5:15 p.m. CDT for portions of eastern Arkansas, northeastern Louisiana, central and northern Mississippi, and western Tennessee.

[21] However, as the update was being issued, a significant supercell evolved across western Mississippi, producing a violent, long-tracked, and deadly high-end EF4 tornado that struck Rolling Fork, Midnight, and Silver City, inflicting catastrophic damage, and causing over a dozen fatalities.

[25][26] To the north, an organized line of convection with embedded supercells moved across Tennessee and Alabama, and although its strength was inhibited by lower moisture and a lack of robust instability, it still produced damaging winds and several additional tornadoes into the early morning hours of March 25, including a low-end EF2 tornado that caused a fatality in the northern part of Hartselle, Alabama.

In this corridor, which extended from Louisiana into western Georgia, CAPE values reaching into the 1500–2000 J/kg range, effective 50-knot wind shear, and elevated dew points were present, allowing for a favorable environment for the re-intensification of the system, and its segmentation into individual supercells.

[citation needed] This violent, deadly high-end EF4 tornado first touched down in Issaquena County southeast of Mayersville near the Mississippi River.

Some of the most violent damage occurred in the northeastern part of town, where a flower shop housed in a well-built brick building was completely leveled at high-end EF4 strength, with its concrete foundation slab being partially swept clean of debris.

Many vehicles were also thrown through the air and mangled, and numerous large trees in and around Rolling Fork were denuded and debarked, and a few of them were completely stripped clean of all bark.

Four manufactured homes were completely destroyed in the center of town, a church sustained roof damage, a large number of old hardwood trees were also snapped or uprooted, and power lines were downed as well.

[41] The tornado then exited Black Hawk and continued northeastward through densely forested areas for about 11 miles (18 km) passing southeast of Coila, causing widespread EF2 to EF3 tree damage.

One of the destroyed mobile homes received a high-end EF2 rating after being ripped off its blocks and thrown 50 yards (46 m) into a nearby wooded area, obliterating it and killing the three occupants inside.

As it approached Robinson-Thompson Road at a slightly stronger low-end EF2 intensity, the tornado destroyed an outbuilding and inflicted minor to moderate roof and siding damage to a 100-year-old home.

It then abruptly weakened and dissipated as it crossed the road well southwest of Lodi after traveling for 29.43 miles (47.36 km) at an average forward speed of 58.9 mph (94.7 km/h).

As the tornado travelled northeast across County Road 179 and US 45 Alternate, it produced EF0 to EF1 damage, snapping and uprooting numerous trees and overturning a metal carport.

The tornado remained at EF2 strength while continuing northeast of Egypt, snapping numerous additional trees and power poles, destroying an outbuilding, and inflicting roof damage to several homes.

The tornado then began to intensify further, attaining high-end EF2 intensity as it reached McAllister Road and Herndon Lane, where several homes suffered significant damage, including a few that had roofs ripped off and some exterior walls collapsed.

[41][67] As the tornado crossed US 45 at the intersection with Whatley Road and passed just south of New Wren, it reached low-end EF3 intensity, inflicting significant damage to numerous structures.

An Exxon gas station, Jack's restaurant, multiple churches, and a Piggly Wiggly grocery store all suffered major structural damage or were destroyed, along with other commercial buildings and businesses in town.

The tornado then weakened slightly but remained strong as it continued northeastward at EF2 strength, causing severe damage to a few homes and a National Guard armory near the Amory Golf Course as it exited town.

[67] This intense tornado touched down just east of the Alabama-Georgia border in Troup County northwest of West Point, Georgia and moved eastward, damaging trees at EF0 strength.

[76][77] Still continuing eastward, the tornado exited North West Point and crossed over a CSX railway line into forested areas, snapping or uprooting a large swath of trees.

Briefly strengthening back to EF2 intensity, the tornado snapped large tree trunks as it crossed Oak Grove Road, and also caused EF1 damage to two residences.

[65] Rolling Fork's funeral director and mayor, Eldridge Walker, said on March 27 that search-and-rescue efforts were "pretty close" to finished and authorities believe everyone has been accounted for.

[89] The Mississippi Emergency Management Agency (MEMA) contracted with the Red Cross to provide survivors with meals and lodging in hotel rooms for up to six months.

[94] Due to the severe damage inflicted to its athletic facilities, Amory High School's baseball team was forced to play the remainder of its season on the road.