The former Arsenal star restored Villa's lead after Ciaran Clark's opener had been cancelled out by Rovers substitute Nikola Kalinic.
Nathan Delfouneso doubled Villa's lead and even a red card after 62 minutes for defender Nathan Baker, after a challenge on Junior Hoilett, failed to halt their progress.
Villa, who knocked Blackburn out of the Carling Cup and FA Cup last season, deserved their place in the last 16 despite manager Gerard Houllier making six changes.
Off the mark: Robert Pires opened his Aston Villa account with the crucial second
Rovers suffered a setback after only10 minutes when Roque Santa Cruz limped out of the action and wasreplaced by Kalinic. Then a minute later Villa went ahead throughClark's fourth goal of the campaign.
Barry Bannan's corner was met perfectly by the central defender, whose header powered past Paul Robinson.
Gabriel Agbonlahor, operating in awide role, showed his pace before setting up a chance for Delfounesowhose volley was only just too high.
Blackburn threatened for the firsttime when former Rovers goalkeeper Brad Friedel beat out a shot from anarrow angle by Hoilett.
Then after 18 minutes Rovers drewlevel through Kalinic. Delfouneso lost possession to Morten GamstPedersen who picked out the run of Michel Salgado, and the Spanishfull-back's low cross was turned home by the Croatian.
Villa were dominating possession andBannan was only just off-target with a 30-yard drive, and after 35minutes Pires restored Villa's lead with his first goal for the WestMidlands club.
No chance: Blackburn keeper Paul Robinson and Michel Salgado fail to keep out Cieran Clark's headed opener
Grant Hanley and Martin Olsson onlyhalf-cleared the ball and the former Arsenal player struck the ballperfectly on the half-volley from 15 yards out into the roof of the net.
Blackburn's reponse was immediate and Friedel produced a fine save to finger-tip away a header from Christopher Samba.
But Villa made it 3-1 three minutes before half-time when Delfouneso headed home a cross from teenager Baker.
The game was flowing from end to end and Olsson crashed a shot against the crossbar.
Houllier made a half-timesubstitution with Stewart Downing replacing Agbonlahor. Villa forcedthree successive corners and, from the third of them, Baker headed justwide at the far post from a Pires centre.
No dispute: Nathan Baker is sent off by referee Lee Probert after a foul on Junior Hoilett
The on-loan Kyle Walker made apowerful 50-yard run and saw his rising shot blocked by Hanley, andDowning's centre picked out Delfouneso at the near post but he couldonly deflect the ball wide.
Blackburn should have reduced the arrears when Keith Andrews headed wide from eight yards out from Hoilett's centre.
Villa were reduced to 10 men after62 minutes when Baker was given a straight red card by referee LeeProbert for a challenge on Hoilett.
Blackburn tried to make the most of their numerical advantage and Hoilett shot over from 10 yards out.
Jason Roberts carved out a chancefor himself but James Collins made a vital tackle as he prepared toshoot, before Downing had two chances to wrap up the game for Villa.
First Robinson parried his shot after a 60-yard run and then blocked his close-range header.
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