With the influence of moderately strong cyclonic flow aloft, the air mass was expected to become unstable across much of the southern Great Plains, Ozarks, and middle Mississippi Valley by the afternoon hours.

Outflow remnants from the previous night and the early day convection across the Ozarks and the middle Mississippi Valley were a factor in severe weather development with the most aggressive heating and destabilization on the western edge of this activity across the southern Great Plains and just ahead of a cold front.

[13] The most intense severe weather activity was expected to come across the southern Great Plains, specifically Central Oklahoma, during the afternoon hours on that Monday.

As such, the Storm Prediction Center issued a moderate risk of severe thunderstorms during the early morning hours of May 20 from southeastern Missouri to north-central Texas.

[11] The Storm Prediction Center issued a tornado watch at 1:10 p.m. Central Daylight Time (CDT) early that afternoon for the eastern two-thirds of Oklahoma, northwestern Arkansas, and portions of north-central Texas.

[17] The thunderstorm quickly attained supercell characteristics, with rotation at the mid-levels of the storm's cloud structure becoming apparent even before it was officially classified as severe, due to the sufficient amounts of wind shear present over central Oklahoma.

As the forecast suggested that the most significant severe weather would occur in the mid-afternoon, around the time classes concluded for the day, many worried parents began arriving at schools throughout Moore and south Oklahoma City to pick up their children in advance of the storms.

[22] The tornado touched down at 2:56 p.m. CDT in northwestern McClain County, near Long Drive to the southwest of the North Country Club Road and SH-37 intersection, roughly 4.4 miles (7.1 km) northwest of downtown Newcastle.

[23] At this point, the tornado began to grow rapidly in size over the course of 2 minutes; the rope-like funnel started to swell into a large stovepipe, before maturing further into a barrel shape.

As the station's news helicopter was capturing live video of the tornado, then-KWTV chief meteorologist Gary England − upon seeing footage of the backup that was being relayed by pilot Jim Gardner − urged drivers caught in the jam that may have been listening to the station's audio simulcast on area radio outlets to use nearby streets to detour out of the tornado's expected track.

[20] The tornado weakened briefly to EF3 strength before re-intensifying to EF4 intensity near Forman Drive, flattening several homes as it moved through mostly rural areas south of Southwest 149th Street.

[28][29] Every building at Celestial Acres was either leveled or swept away at EF4 intensity, the ground on the property was scoured to bare soil, debris from structures was granulated, and vehicles were thrown and stripped down to their frames.

Surveyors noted that based on the contextual damage, the tornado was likely at EF5 intensity in this area, though the construction quality of the affected buildings only permitted an EF4 rating.

[24][4][30] The tornado continued east, heavily scouring an open grassy field before impacting Briarwood Elementary School, which was completely destroyed.

[24][31][32] Two 12,000-gallon water tanks that were also swept off of the Orr Family Farm grounds were thrown into this area; the roof of Briarwood Elementary was struck by one of them − potentially aiding in compromising the building's structural integrity as it bent the steel girders that held up the roof − shortly before the main vortex struck the building, while the other fell onto and destroyed a home a few blocks east of the school.

[4][34] The tornado continued generally northeast at EF4 strength, completely debarking trees and leveling entire neighborhoods as it moved into the western city limits of Moore.

[35] One anchor-bolted home that was reduced to a bare slab in this area was initially rated EF5, but was later downgraded to EF4 as closer inspection of the foundation revealed that the anchor bolts were missing their nuts and washers.

[23] The tornado then destroyed Plaza Towers Elementary School at EF4 intensity, where seven children were killed when a cinder block wall collapsed on top of them.

[4][31] A bowling alley in the area was leveled,[31] and a 7-Eleven which was on the northern part of the damage path, was completely flattened with four people killed inside (including a three-month-old infant).

[31] The tornado regained EF4 intensity on the other side of the Interstate as it tore through several neighborhoods and destroyed numerous additional homes (though the EF4 damage swath was narrower at this point).

[31] A large grassy field between two subdivisions in this area was scoured to bare soil, with wind-rowed structural debris and several mangled vehicles strewn to the east.

[4] The tornado then began to rapidly narrow and weaken, snapping and uprooting several trees and causing EF2 damage to a farm just east of Moore, where the house lost its roof and an outbuilding was destroyed.

Many students and teachers took shelter in bathrooms and closets, but in a newer addition to the building which housed the school's second and third grade classrooms, seven fatalities occurred.

[55] In addition to erroneous reports concerning the status of Briarwood and Plaza Towers students, various reports regarding fatality and injury counts as well as persons unaccounted for were circulated by traditional and social media outlets in the immediate hours after the tornado struck, which could not immediately be confirmed or refuted due to communications disruptions in the affected areas or were the result of incorrect counting due to miscommunication of estimates.

Upon the office's discovery that some victims were mistakenly counted twice due to communication errors made by Moore rescue response units that the bodies were admitted to area funeral homes (nearly all of the deceased were actually transported to the examiner's office in Oklahoma City), the actual number was revised downward and later confirmed at 24 tornado victims.

[64] On May 6, 2018, nearly five years after the tornado, a 14-year-old survivor who suffered posttraumatic stress disorder after losing seven of his friends at Plaza Towers Elementary School committed suicide.

Governor Mary Fallin requested assistance from then-President Barack Obama[68] who declared a major disaster in the state and ordered federal aid to the affected areas.

[90] Moore Mayor Glenn Lewis stated that he would attempt to get an ordinance passed requiring storm shelters or safe rooms in new housing projects.

The benefit was hosted by country singer and Oklahoma native Blake Shelton and featured performances from Miranda Lambert, Vince Gill, Reba McEntire, Rascal Flatts, Usher, Darius Rucker and Luke Bryan.

[93] The Moore City Council proposed a measure making twelve changes to its residential building codes, include requiring that new home construction in the city include hurricane clips or framing anchors, continuous plywood bracing and wind-resistant garage doors in order for homes to withstand winds up to 135 miles per hour (217 km/h) (equivalent to a high-end EF2 tornado).