A close-range Joseph Mendes finish put the Royals ahead and Jordan Obita's intended cross doubled the lead.
With chances coming at both ends, Michael Kightly and Ben Turner went close for the Brewers but Yann Kermorgant's strike made it 3-0.
Turner and Cauley Woodrow replied but Lewis Grabban sealed Reading's win.
Turner's tap-in and Woodrow's header from Will Miller's cross looked like teeing up a nervy finale, but substitute Grabban netted following a goalmouth scramble with five minutes left.
The Royals will face sixth-placed Fulham in the two-legged play-off semi-finals, with the first leg at Craven Cottage on Saturday, 13 May and the return fixture on Tuesday, 16 May.
Burton, who had already secured their Championship status, dropped to 20th in the table, one point above the relegation zone.
Burton boss Nigel Clough:
"I thought we deserved more than a defeat from the game. We played well throughout the game. The first goal was messy and a bit scrappy early on but the second goal was as good as you will see all season.
"With all the other results going the way that they did today it just goes to show how massively important that point was for us at Barnsley a week ago.
"They were a bit more clinical than us today. That is why they are third in the league and may be in the Premier League in a few weeks' time."
Reading manager Jaap Stam:
"It is always nicer when you can go into the play-offs with a win. We are very happy.
"It is going to be two very interesting games against Fulham now. They are a very good side but so are we.
"Burton made us work hard for it. We knew that with it being their last home game they wanted a result and they made it difficult for us. I thought we scored four very good goals today to win the game."
Match ends, Burton Albion 2, Reading 4.
Second Half ends, Burton Albion 2, Reading 4.
Attempt missed. Cauley Woodrow (Burton Albion) right footed shot from outside the box is too high from a direct free kick.
Hand ball by George Evans (Reading).
Foul by Luke Varney (Burton Albion).
Liam Moore (Reading) wins a free kick in the defensive half.
Attempt blocked. Cauley Woodrow (Burton Albion) right footed shot from the left side of the box is blocked.
Attempt blocked. Marvin Sordell (Burton Albion) left footed shot from outside the box is blocked.
Attempt blocked. Luke Varney (Burton Albion) right footed shot from the right side of the six yard box is blocked.
Attempt saved. Cauley Woodrow (Burton Albion) left footed shot from the left side of the box is saved in the centre of the goal. Assisted by Jackson Irvine with a through ball.
Foul by John Brayford (Burton Albion).
Danny Williams (Reading) wins a free kick in the defensive half.
Attempt saved. Yann Kermorgant (Reading) header from the centre of the box is saved in the bottom left corner.
Attempt saved. Danny Williams (Reading) right footed shot from a difficult angle on the left is saved in the centre of the goal. Assisted by Chris Gunter with a cross.
Attempt blocked. Lewis Grabban (Reading) right footed shot from the centre of the box is blocked. Assisted by Liam Kelly.
Foul by Luke Varney (Burton Albion).
Tiago Ilori (Reading) wins a free kick on the right wing.
Attempt missed. Marvin Sordell (Burton Albion) left footed shot from the centre of the box is too high.
Goal!  Burton Albion 2, Reading 4. Lewis Grabban (Reading) right footed shot from very close range to the top right corner following a corner.
Attempt saved. George Evans (Reading) right footed shot from the centre of the box is saved in the centre of the goal.
Attempt missed. Liam Kelly (Reading) right footed shot from the centre of the box is close, but misses to the left following a corner.
Yann Kermorgant (Reading) hits the bar with a header from the right side of the six yard box. Assisted by Jordan Obita with a cross following a corner.
Corner,  Reading. Conceded by Joe Sbarra.
John Brayford (Burton Albion) wins a free kick in the defensive half.
Foul by Yann Kermorgant (Reading).
Jackson Irvine (Burton Albion) wins a free kick on the left wing.
Foul by George Evans (Reading).
Cauley Woodrow (Burton Albion) wins a free kick in the defensive half.
Foul by Joey van den Berg (Reading).
Attempt blocked. Yann Kermorgant (Reading) left footed shot from the centre of the box is blocked. Assisted by Liam Kelly with a cross.
Corner,  Reading. Conceded by Ben Turner.
Substitution, Burton Albion. Luke Varney replaces Will Miller.
Jackson Irvine (Burton Albion) is shown the yellow card for a bad foul.
Foul by Jackson Irvine (Burton Albion).
Liam Kelly (Reading) wins a free kick on the right wing.
Substitution, Reading. Danny Williams replaces Roy Beerens.
Goal!  Burton Albion 2, Reading 3. Cauley Woodrow (Burton Albion) header from the centre of the box to the bottom right corner. Assisted by Joe Sbarra.
Goal!  Burton Albion 1, Reading 3. Ben Turner (Burton Albion) left footed shot from the left side of the six yard box to the bottom left corner. Assisted by Lloyd Dyer following a corner.
Corner,  Burton Albion. Conceded by Ali Al Habsi.
Substitution, Burton Albion. Joe Sbarra replaces Luke Murphy.
Reading withstood a Burton Albion comeback to secure third place in the Championship with a thrilling final-day victory at the Pirelli Stadium.