The serie A side enjoyed a 2-1 victory in the Santiago Bernabeu for a 4-2 aggregate triumph, leaving Madrid going out at the last-16 stage again, as they did last season at the hands of Bayern Munich. Real follow seven-time winners AC Milan, the reigning champions who were unceremoniously ousted Tuesday by Arsenal, as casualties in the first knock-out round of the competition. The Spanish champions, who last won the trophy in 2002, had defender Pepe sent off after a second yellow card in the 71st minute as they slid to defeat.
Roma twice struck the post or bar - through a long-range Alberto Aquilan effort and a Mirko Vucinic header in each half - before Rodrigo Taddei headed the opening goal two minutes after Pepe's dismissal.
Raul Gonzalez got Real back into the game two minutes after but Vucinic - a 65th-minute substitute - made absolutely sure in stoppage time with a header from a Christian Panucci free-kick which this time sailed in under the bar.
Real's defeat and Tuesday's exit of Sevilla on penalties to Turkey's Fenerbahce leaves Barcelona as the only Spanish team left in the competition.
Chelsea joined Premier League rivals Arsenal and Manchester United into the quarter-finals with a comfortable 3-0 victory over Greek side Olympiakos.
Meanwhile 2004 winners Porto bowed out to Germany's Schalke 04 in a penalty shoot-out in which 21-year-old keeper Manuel Neuer was the hero for the Bundesliga side.
Neuer stopped two penalties in the shoot-out and made a series of outstanding saves in regular time as the Germans progressed to the quarter-finals for the first time, 4-1 on penalties after the tie had finished 1-1 on aggregate after 90 minutes and extra-time.
Lisandro Lopez scored for Porto four minutes from time to cancel out the visitors' 1-0 home win. The goal came four minutes after Porto's Jorge Fucile was sent off for a high lunging tackle in midfield on Levan Kobiashvili.
The Bundesliga side, coming off three straight defeats in the league, were on the back foot throughout and had Neuer to thank for keeping out the home side, who created and wasted chances.
In the shoot-out he thwarted Bruno Alves and Lisandro Lopez, while Schalke kept their nerve to convert all their spot kicks.
Goals from Michael Ballack, Frank Lampardand Salomon Kalou extended Chelsea's unbeaten home run to 60 matches to put the Blues into the last eight for the fourth time in the last five seasons.
After the goalless draw in Greece two weeks ago, Germany midfielder Ballack got Chelsea off to a perfect start when he headed in Lampard's cross from close range in the fifth minute.
Lampard then mopped up from close range 20 minutes later after goalkeeper Antonis Nikopolidis could only parry a Ballack shot.
Kalou made it three from close range three minutes after the break when the visitors failed to deal with a Lampard corner headed on by Ricardo Carvalho.
England could have four teams in the last eight if Liverpool prevail at Inter Milannext Tuesday, holding a 2-0 lead from the first leg.
The draw for both the quarter-finals and semi-finals will be held on March 14. The first legs of the quarter-finals will be played on April 1 and 2, with the return legs on April 8 and 9.