Arsenal named a strong side captained by Mesut Ozil while Real had Bale on the bench and Eden Hazard, wearing the number 50 shirt, starting alongside fellow new signing Luka Jovic in attack.
Manchester United will be out for revenge against Benfica on Tuesday in their Champions League match.
Barcelona's march towards the Primera Liga title slowed on Saturday after a goalless draw with bottom-placed side Malaga.
Spurs beat Ajax 3-2 in the second leg of the semi-final on Wednesday and will face Liverpool on June 1 in Madrid.
They beat Vitoria Guimaraes 2-0 in the Portuguese Premier League on Thursday.
Its Chelsea vs Barcleona, Real Madrid vs Arsenal in the Champions League
Manchester United must end a surprising three-match scoring drought to avoid Champions League elimination in Lisbon.
Manchester United visit Lille in the Champions League on Wednesday with manager Alex Ferguson under extreme pressure following Saturday's 4-1 thrashing at Middlesbrough.
Bundesliga leaders Bayern Munich were made to work extremely hard for a 3-1 victory at VfB Stuttgart on Saturday that sent them eight points clear at the top of the table with five games left.
Barcelona coach Frank Rijkaard says his side will face a daunting task when they take on his former club AC Milan in the Champions League semi-finals.
The Dutch striker scored five minutes from time to earn Manchester United a 2-1 win over Benfica in the Champions League.
Arsenal will have to produce the biggest second leg comeback in a Champions League knockout tie to avoid a seventh successive exit at the last 16 stage when they host Bayern Munich on Tuesday.
Goals by Cesc Fabregas and Thierry Henry gave Arsenal an impressive 2-0 home win over Juventus
The 30-year-old joins Luke Shaw in the treatment room after the left back pulled out of the England squad with an injury on Monday.
Champions Liverpool were sent crashing out by Benfica.
Thierry Henry scored with a brilliant individual effort to give the English side a 1-0 victory in the first leg last 16 knock-out round.
PSV goalkeeper Gomes misjudged a 25-metre free kick from Juninho as the Dutch side went down 0-1.
Andriy Shevchenko struck with a penalty to give AC Milan a valuable 1-1 draw in the Champions League last 16 first leg match against Bayern Munich.
Juan Mata praised Jose Mourinho's remarkable knack for coming out on top on the biggest occasions after Manchester United beat Ajax Amsterdam 2-0 on Wednesday to signal the Portuguese coach's 12th triumph in a final from 14 attempts.
The Champions League group stages took on a less predictable look after Thursday's draw, helped by UEFA's decision to tweak the seeding system.
Lionel Messi assumed the rare role of fan on Thursday conveying his best wishes to his idol and Argentina great Pablo Aimar who retired on Wednesday.
IMAGES from the Europa League matches played on Thursday
Paris St Germain extended their Ligue 1 lead to 13 points with a 4-3 home victory against Girondins de Bordeaux on Sunday but the French champions were again exposed at the back and had Neymar sent off. A Marquinhos double, Edinson Cavani's 200th PSG goal and a goal by Kylian Mbappe put the capital side on 65 points from 26 games but they lost captain Thiago Silva to a muscle injury and Neymar picked up a straight red card for a late challenge in stoppage time.
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The Italians drew 2-2 in Greece against Egaleo, a result which sends Middlesbrough, Villarreal and Partizan Belgrade through as the three qualifiers from Group E.
United are unbeaten in all competitions since Solskjaer replaced Jose Mourinho in December and their improvement is down to the Norwegian's insistence on an attacking style of play, as opposed to the defensive fare served up by his predecessor.
Luka Modric pulled one back for Zinedine Zidane's shellshocked side with a brilliant strike from distance early in the second half before substitute Vinicius Jr reduced the deficit to one goal.
Juventus scraped a 2-2 draw with Swedish underdogs Djurgarden, while Liverpool strolled to a 2-0 win at Graz AK in the Champions League's third qualifying round.
Lionel Messi was in inspired form as champions Barcelona hammered Celta Vigo 5-0 on Saturday, recording a fourth straight league victory which keeps them top of La Liga after Real Madrid had put the pressure on the Catalans with a 4-1 win at Eibar.
'You realise the fear when Barcelona could get knocked out. It would hurt UEFA a lot. I don't know what they have to do for someone to send one of them off'
Higuain had a disappointing Copa America tournament in July, scoring two goals during the competition and missing his spot kick as Argentina lost on penalties to Chile in the final.
Pep Guardiola will return to the Nou Camp in the Champions League group stage after his new club Manchester City were drawn against his former Barcelona team on Thursday. The two sides were drawn in Group C alongside Borussia Moenchengladbach and former European champions Celtic in one of the toughest of the eight sections. Spanish coach Guardiola, who won the Champions League twice with Barca, faced the Catalans when he was in charge of Bayern Munich two seasons ago and suffered a 5-3 defeat in the semi-finals.
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