The Bees took the lead within 11 minutes thanks to Martin Jensen, shooting through the legs of Rafael as it fumbled in.
Mbeumo then added the second 12 minutes later, driving in off the right-hand side and curling a beautiful shot with his left foot into the bottom left corner.
More misery was piled on the Royals by Mbeumo just six minutes later, as he picked up the ball on the edge of the box, turned, and punished Reading's woeful d, again with his left foot.
Reading did manage to get a goal back in the 64th minute through substitute Sone Aluko, who guided the ball into the bottom right corner with his head with just under an hour to go.
Unfortunately for the away side, they couldn't get those extra two goals to see them get a point. They now drop out of the play-offs into eighth, while Brentford rise to fourth.
Story of the match
Brentford came into this game on a fantastic run of form, unbeaten in 12 games before this. They made two changes from their 1-1 draw with Watford, Charlie Goode coming in for the suspended Ethan Pinnock, while Tarique Fosu filled in at right-back in place of Henrik Dalsgaard.
Reading on the other hand has got back on track in some ways, however, had just come back off a loss against league leaders Norwich City. The Royals made two changes to that side, Lewis Gibson and Sone Aluko being dropped for Tomas Esteves and Sam Baldock, with Gibson picking up an injury in the first half on Wednesday night, which forced him out of the squad.
The first real chance came from Brentford who took the lead in the 11th minute, Sergi Canos flicking the ball past two defenders to a free-running Martin Jensen, who fired a shot that deflected off Michael Morrison's heel and then fumbled in through Rafael's legs. A bright start for the Bees, who would look to build on that goal with some more.
The first few decent chances for Reading came nine minutes later, an in-swinging free-kick from Michael Olise ends up going out for a corner after Tom Holmes couldn't quite get his feet sorted in time, and it deflected off the defender. The resulting corner was whipped in and captain Liam Moore volleyed it straight at David Raya in the Brentford net.
Brentford then doubled their lead through Bryan Mbeumo, who received the ball on the right-hand side, driving inside with Esteves allowing him too much space and he curled it into the bottom left corner to give Brentford a comfortable lead after 22 minutes.
Six minutes later Brentford added a third, Mbeumo picking up the ball near the centre of the edge of the box, turned onto his left foot, and drove the ball into the bottom right corner to add his second of the day inside half an hour.
Reading had the better of it towards the end of the first half, with a good chance coming again in the 38th minute when Josh Laurent was slipped through by Ovie Ejaria on the left-hand side, he then shot near post and it was well saved by Raya.
At half-time, the away side looked down and out, and they were going to need to come out all guns blazing if they were going to get something from this game. Brentford made one change, Rico Henry coming off for Dominic Thompson.
But it was the Bees who started the better, as they kept on pressing for a fourth. Reading did have some fight though to get back into the game, forcing a save from Raya early on as Ejaria struck it near post, forcing a quick reaction save from the Spaniard.
On the hour mark, the Royals made their first change, Sone Aluko coming on for loanee Alfa Semedo and he made an instant impact, Olise crossing to an open Aluko who nodded it in the bottom right corner to give Reading a glimmer of hope, and Olise' seventh assist of the season.
Brentford made a double change in reaction to the goal, Emiliano Marcondes, and Saman Ghoddos coming on for Josh Dasilva and Bryan Mbeumo. Sergi Canos joined them in coming off five minutes later, as he was replaced by Marcus Forss, as they looked to see out the game.
There was a penalty shout for Reading when former royal Tarique Fosu brought down Sone Aluko in the box, but it was a clean tackle and the referee waved it away. Reading then kept pressing, Ejaria forcing a save from Raya before the ball was whipped in at the back post for Holmes who forced another save from Raya before he claimed the ball yet again as Reading wasted another good chance.
Ivan Toney then nearly added his seventeenth of the season with a header just going past the post from a corner. With all these chances from either side, you thought there would be another goal in this game.
Going into the closing stages, Reading kept pushing for a second, with Brentford providing a real threat on the counter-attack. Reading needed substitutions but was reluctant to make any, only making one going into the 90th minute. With five minutes added on, time was running out.
Brentford nearly got their fourth through Ivan Toney hit the crossbar with a header from a corner, but the three goals from the Bees were enough to seal all three points.
Man of the match: Bryan Mbeumo (Brentford)
The fantastic Frenchman scored a brace, that is enough said. He was brilliant off the right-hand side, causing Esteves a lot of problems with his wonder of a left foot, and was unstoppable.