Luton saw their Championship survival hopes severely dented as four goals from Yakou Meite helped Reading to a first win in four games.
The Hatters remain rooted to the foot of the table after their six-match unbeaten run was brought to an abrupt conclusion.
Two goals in the space of two minutes for Meite put Reading in command before he completed his hat-trick in the space of just 18 minutes before half-time.
George Puscas headed in a fourth early in the second half before laying on Meite for his fourth and Reading's fifth soon after, the Ivorian scoring with a well-taken finish.
Reading's biggest Championship victory since January 2014 eased any lingering relegation concerns they may have had after losing two of their three games since the season resumed.
But the chastening defeat for Nathan Jones' side and results elsewhere, left Luton five points adrift of safety with five games to play.
Their fate may well be determined by the outcome of their next two fixtures, against fellow relegation contenders Barnsley and Huddersfield, starting at home on Tuesday against the Tykes before a trip to west Yorkshire three days later.
Jones will have his work cut out to lift morale after seeing his side fall to a heaviest home league defeat since May 2007.
Meite's memorable afternoon The afternoon belonged to Ivory Coast international Meite, who almost opened his account inside the first 10 minutes, only to be denied by Dan Potts' goalline clearance after the rebound fell to him following a Simon Sluga save.
Luton were twice out of luck when James Collins headed Harry Cornick's cross against the bar and Matty Pearson had an appeal for a penalty turned away when he appeared to be brought down by Ovie Ejaria.
Shortly after, Reading and Meite punished them twice as he first slotted in a Puscas through ball and then capitalised on Luton goalkeeper Sluga and right-back Pearson's failures to clear a Gabriel Osho cross and a Puscas shot.
Meite did not have to wait long to complete his first Reading hat-trick as Ovie Ejaria threaded a pinpoint ball through the defence for him to finish from the edge of the six-yard box.
Chances continued to come the visitors' way after the break as John Swift had a shot inside the penalty area turned behind for a corner but Puscas grabbed the fourth after Michael Morrison's header back across goal.
And Meite completed the rout when set free 30 yards out for a one-on-one with the keeper.
Luton Town manager Nathan Jones: "That performance was totally out of character and some of the worst defending I have ever seen in my time in management, certainly in my two spells here.
"It's very difficult for me to have a go at my players today, because these are unprecedented circumstances we find ourselves in, but these home games were opportunities we needed to take.
"The intensity around our press and around the ball were nowhere near what they needed to be.
"It's going to be all about recovery and maintenance between now and Tuesday (against Barnsley).
It's as big a week as this football club's had in a long time and we have to take points from those next two games because if we don't, our fate could be sealed.
" Reading manager Mark Bowen: "We made some changes from the defeat by Brentford and for me, today was about being more pro-active than reactive to things, being on the front foot.
"While winning 5-0 is fantastic, the more pleasing thing for me is keeping concentration right to the end and ensuring we didn't switch off and we held on to a clean sheet.
On Meite: "He came to see me yesterday in my office, putting a case across for him to play more as a number nine and a central striker, but I said to him I feel he can find more space in the wide areas and create more chances.
"He looked across at me in the changing room afterwards with a wry smile and a grin so maybe I won that particular argument this time.