The U's were reduced to 10 men early on after Joe Edwards was sent off for a late challenge on Matty Palmer.
Lucas Akins' close-range finish put the Brewers ahead on the stroke of half-time despite protests of offside.
Akins then completed his hat-trick after the break with a thumping finish from the edge of the box followed by a clean strike into the bottom corner.
Colchester's relegation comes towards the end of a hugely disappointing season which saw them fail to register a league win in more than four months between late October and early March.
The winless run of 19 matches was finally broken when they beat Bradford on 1 March, but by then they were already rock bottom.
A slight upturn in form over the last few weeks, in which they won three and drew two out of six games, saw Colchester move off the foot of the table.
However, with 95 goals conceded, they could become the first team to let in 100 league goals since Stockport County shipped 102 in the old First Division in 2001-02.
Burton, who came up from League Two last campaign, are now on the verge of winning back-to-back promotions as they sit six points clear of the play-offs in second, with two matches left.
Match ends, Colchester United 0, Burton Albion 3.
Second Half ends, Colchester United 0, Burton Albion 3.
Attempt saved. George Moncur (Colchester United) right footed shot from the centre of the box is saved in the centre of the goal.
Attempt missed. Owen Garvan (Colchester United) right footed shot from outside the box is close, but misses to the left.
Mason Bennett went off injured after Burton Albion had used all subs.
Foul by Mason Bennett (Burton Albion).
Alex Wynter (Colchester United) wins a free kick in the attacking half.
Substitution, Colchester United. Drey Wright replaces Chris Porter.
Foul by Callum Butcher (Burton Albion).
George Moncur (Colchester United) wins a free kick in the defensive half.
Substitution, Burton Albion. Mason Bennett replaces Matthew Palmer.
Attempt missed. Tyler Walker (Burton Albion) header from the centre of the box misses to the right.
Attempt saved. George Moncur (Colchester United) left footed shot from the centre of the box is saved in the centre of the goal.
Attempt saved. Chris Porter (Colchester United) left footed shot from outside the box is saved in the bottom left corner.
Substitution, Burton Albion. Tyler Walker replaces Stuart Beavon.
Mark Duffy (Burton Albion) wins a free kick in the defensive half.
Foul by Alex Wynter (Colchester United).
Corner,  Burton Albion. Conceded by Elliot Parish.
Attempt saved. Mark Duffy (Burton Albion) right footed shot from the left side of the box is saved in the bottom left corner.
Substitution, Burton Albion. Callum Butcher replaces Damien McCrory.
Attempt missed. Hamza Choudhury (Burton Albion) right footed shot from outside the box misses to the right.
Corner,  Burton Albion. Conceded by Tom Eastman.
Corner,  Burton Albion. Conceded by Nicky Shorey.
Attempt blocked. Lucas Akins (Burton Albion) right footed shot from the right side of the box is blocked.
Tom Lapslie (Colchester United) is shown the yellow card for a bad foul.
Mark Duffy (Burton Albion) wins a free kick in the attacking half.
Foul by Tom Lapslie (Colchester United).
Goal!  Colchester United 0, Burton Albion 3. Lucas Akins (Burton Albion) left footed shot from the right side of the box to the bottom left corner. Assisted by Jon McLaughlin.
Hand ball by Stuart Beavon (Burton Albion).
Attempt missed. Tom Lapslie (Colchester United) right footed shot from outside the box is just a bit too high.
Goal!  Colchester United 0, Burton Albion 2. Lucas Akins (Burton Albion) left footed shot from the centre of the box to the high centre of the goal. Assisted by Stuart Beavon.
Attempt missed. Alex Wynter (Colchester United) right footed shot from outside the box is close, but misses to the left.
Second Half begins Colchester United 0, Burton Albion 1.
Substitution, Colchester United. George Moncur replaces Louis Dunne.
First Half ends, Colchester United 0, Burton Albion 1.
Corner,  Burton Albion. Conceded by Alex Wynter.
Attempt blocked. Mark Duffy (Burton Albion) right footed shot from the left side of the box is blocked.
Goal!  Colchester United 0, Burton Albion 1. Lucas Akins (Burton Albion) right footed shot from very close range to the bottom left corner. Assisted by Mark Duffy.
Corner,  Burton Albion. Conceded by Nicky Shorey.
Hamza Choudhury (Burton Albion) wins a free kick in the defensive half.
Colchester were relegated from League One with a home defeat by Burton, who boosted their own promotion chances.