Shane Long put the Royals ahead from the penalty spot after Leon Cort, who was later sent off, brought him down.
Jobi McAnuff's measured second-half effort, as well as goals from Michael Antonio and Simon Church ensured Reading claimed their first win away from home since a 2-1 victory at Leicester in August.
Reading crowded the midfield during the early stages in an attempt to stifle the hosts. And as a result the Clarets were limited to a tame Chris Iwelumo header during the opening exchanges.
Burnley goalkeeper Brian Jensen was forced to punch an inswinging Ian Harte cross to safety in the fifth minute and Andre Bikey did well to block Jay Tabb on the follow-up.
But the visitors forged ahead a minute later when the isolated Long got the upper hand on Cort.
The Clarets defender was clearly caught out for pace as Long wriggled his way goal-side.
Cort's challenge had to be perfectly timed but was not, and there were few complaints as referee Nigel Miller pointed to the spot and brandished a yellow card.
Long took the kick himself and, although Jensen guessed the right way, the ball found the bottom right-hand corner.
Matthew Mills did just enough to distract Iwelumo in the 19th minute as he stretched to get on the end of Wade Elliott's testing cross.
Long almost doubled the away side's advantage in the 23rd minute when the bounce of Mills' defensive clearance deceived Bikey.
However, with the angle tightening and Bikey doing his best to make up the lost ground, Long could only ripple the sidenetting.
The hosts saw penalty claims of their own waved away by Miller in 38th minute after Mills came across Iwelumo, who had charged on to a cleverly-weighted pass from Elliott.
Jay Rodriguez's deflected shot forced Reading goalkeeper Adam Federici, who had already made his dive and had to adjust late, into a save at full stretch on the stroke of half-time.
Hal Robson-Kanu wasted a glorious chance for the visitors with seven second-half minutes gone.
McAnuff slid the ball through for the overlapping Royals winger who dragged his shot across the face of goal.
The chances were coming thick and fast for Burnley, Chris Eagles seeing a curling effort from 25 yards beat away by Federici, while he should have hit the target with a volley which followed and failed miserably with a snap-shot after Mills' miscued clearance.
Reading then left Burnley with a mountain to climb in the 64th minute when McAnuff tucked home from the edge of the box.
Cort got his head to a Harte free-kick, but as it dropped on the edge of the box, McAnuff calmly side-footed beyond Jensen.
Cort's second career red card then followed in the 67th minute after he clattered into Long.
But for two superb stops from Jensen the scoreline could have been far worse for Burnley.
The Dane repelled Long, who had gone through one-on-one, and then palmed McAnuff's more calculated strike wide of goal.
Substitute Antonio used his first touch to roll the ball in from point-blank range after Long's pull-back four minutes from time.
And Church belted home a fourth deep into stoppage-time to seal the win.