Mourinho's Real adventure heads back to Milan
However, Mourinho, who masterminded Inter Milan's first triumph in the competition for 45 years in May after taking Porto to the pinnacle in 2004 will visit AC Milan rather than Inter at their shared San Siro home stadium on November 3.
Real (9 wins) and Milan (7) are the two most successful European Cup winners and were drawn together in Group G along with four-time winners Ajax Amsterdam and French side Auxerre.
New Milan coach Massimiliano Allegri agreed the group would be tough.
"Certainly we will be pumped up to face Real," Allegri told the club website. "The San Siro and Bernabeu will be rocking. A spectacle is assured."
Inter, under their new boss Rafa Benitez, will face Werder Bremen and Champions League debutants Tottenham Hotspur and Twente Enschede of the Netherlands in Group A, Spurs being one of three London sides in the competition and familiar foes to Benitez from his time with Liverpool.
Barcelona, European champions in 2009, will face Panathinaikos, FC Copenhagen and Rubin Kazan of Russia in Group D, looking to avenge a shock home defeat to the Russians who beat them 2-1 at the Nou Camp in the group stage last season.
Manchester United, winners in 2008 face Valencia, Rangers and Bursaspor of Turkey with the Rangers match especially poignant for United boss Alex Ferguson, who once played for Rangers and still has close links with his home city of Glasgow.
United are among the quartet of English clubs including Arsenal, Chelsea and Spurs who all have extra incentive to lift the European Cup this season with the final at Wembley in May.
Arsenal's chief executive Ivan Gazidis was already eying a place there after his club were drawn against Braga, Shakhtar Donetsk and Partizan Belgrade.
STEEL AND EXPERIENCE
"We have a real incentive to win it this year with the final at Wembley. We have added steel and experience to the side and we are one year older and more experienced and are going for it," Gazidis told reporters.
Chelsea, who are familiar visitors to Wembley having won the last two FA Cups there, return to Moscow where they lost the 2008 final to Manchester United, with a match against Spartak.
Chelsea also face Zilina of Slovakia and Olympique Marseille, with their talismanic striker Didier Drogba no doubt relishing two battles against his old club.
Bayern Munich, who lost May's final to Inter, will face AS Roma, Basel and CFR Cluj.
Real Madrid and Milan's rivalry goes back to the first season of European competition in 1955-56 when Real beat Milan in the semi-finals and in all they have played each other 13 times with Milan winning six times and Real five.
Ajax have also enjoyed memorable final showdowns with Milan, with the Italians triumphing in 1969 and the Dutch in 1995.
While Real, Milan and Ajax will be looking to revive old glories, Inter will be seeking to become the first club to retain the European Cup in the Champions League era.