Brentford slotted in three first-half goals to breeze past the Royals and overtake them in the Championship table.
A howler Rafael saw Reading go a goal down to Mathias Jensen’s effort, before Bryan Mbeumo netted a brace before the half hour mark to put the Bees in control.
Sone Aluko came off the bench to head in what was just a consolation goal in the second half as the Royals fell to a second consecutive defeat.
Reading dropped out of the play-off places and down to eighth in the table as Brentford climbed up to fourth.
Veljko Paunovic was forced into more changes as the injuries continue to tumble in the Royals squad as Lewis Gibson became the latest absentee.
The Royals were without firepower in attack as Lucas Joao and Yakou Meite both remain injured and aren’t expected back until the new year.
The Bees started fast and took the lead after just 11 minutes after a drop in concentration from Rafael whose mistake cost Reading.
Brentford worked the ball down the left and found the run of Mathias Jensen, who was left free by Andy Rinomhota and Sam Baldock.
Despite hitting a tame shot towards Rafael at his near post, but the Brazilian made a mess of the shot as it squirmed through his body and into the back of the net.
Michael Olise sent a dangerous free kick into the box to test the Brentford defence and find a Reading shirt but the hosts defended well to head clear for a corner. From the resulting set piece, Liam Moore clawed a shot at goal on the volley but David Raya made a comfortable save.
Just minutes after that chance, Brentford went down the other end of the pitch and doubled their lead.
This time Rafael had no chance of stopping the shot. A diagonal long ball found Bryan Mbeumo on the right wing who skipped past Tomas Esteves on to his left foot and sent a rocket into the far left corner from the edge of the box.
And things went from bad to worse for the Royals who found themselves three goals down within half an hour.
Brentford sliced through Reading’s casual defending with a slick one touch passing move as Ivan Toney slipped the ball to Mbuemo who opened up his body and bent the ball into the bottom right corner.
Reading had a half chance before the break as Josh Laurent soared through the midfield on a solo mission and hit a shot at Raya, which was collected easily enough to continue the frustrating half.
Jensen picked up the first yellow of the day for a cynical foul on Olise in the only blip on an otherwise superb half for the home side who went into the break with a three goal lead.
With no signs of a comeback likely in the opening 15 minutes of the half, Sone Aluko was brought on to replace Semedo.
And the substitute made an instant impact. With 64 minutes on the clock, Aluko put Reading on the scoresheet as he was left unmarked in the middle and nodded the ball past Raya from Olise’s cross to put the Royals on the scoresheet.
The Bees had a chance to add a fourth and wrap the game up once and for all, but Tom Holmes was determined to not let that happen and made a crucial sliding tackle to win the ball in the box.
Reading couldn’t salvage any further signs of a comeback despite a much improved second half performance as they fell out of the top six of the table.
The Royals host Luton Town at the Madejski on Boxing Day in their next fixture.
Brentford: Raya, Fosu-Henry, Goode, Bech Sorensen, Henry, Jensen, Janelt, Dasilva, Mbeumo, Toney, Canos
Subs: Thompson, Norgaard, Marcondes, Forss, Ghoddos, Daniels, Pressley, Haygarth
Reading: Rafael, Esteves, Morrison, Moore, Holmes, Laurent, Rinomhota, Olise, Semedo, Ejaria, Baldock
Subs: McIntyre, Southwood, Aluko, East, Melvin-Lambert, Bristow, Watson, Onen, Dorsett
Goals: Jensen 11′, Mbuemo 23′, 29′, Aluko 64′
