With Premier League leaders Chelsea on top form, Manchester City will be hoping their Champions League win over Bayern Munich boosts confidence and re-ignites their title defence when they visit high-flying Southampton on Sunday (1900 IST) .
Images from the Champions League matches played across Europe on Wednesday.
On a night of close finishes in all five first-leg playoff games, the 21-year-old Dutch winger opened his United account with a memorable performance in the famous number seven shirt previously worn by George Best, Eric Cantona and David Beckham.
Last season's runners-up Liverpool, big-spending French league champions Paris St Germain and Carlo Ancelotti's Napoli were thrown together in the pick of the groups while holders Real Madrid must face last season's semi-finalists AS Roma.
Real Madrid failed to win their Champions League group for the first time in four years when a late goal by substitute Marco Reus allowed Borussia Dortmund to equalise and clinch a 2-2 draw.
In other matches, VfL Wolfsburg edged past Hertha Berlin 2-0; promoted Ingolstadt snatched a last-gasp 1-0 win at Werder Bremen
It was the ninth consecutive victory for Dortmund in all competitions this season and showed they had put last season's disappointing performances behind them.
An in-form Bayern Munich will be looking to notch up their fourth straight win in the Champions League group stage and seal a spot in the final 16 when the Bundesliga champions face Viktoria Plzen on Tuesday.
It is a mark of how far Tottenham Hotspur have come that they start as favourites to win what could be a pivotal Champions League Group E fixture away to Bayer Leverkusen on Tuesday despite the absence of key defender Toby Alderweireld.
It compounded a woeful few months for the club as coach Julen Lopetegui came and went before former player Santiago Solari replaced him in November. They sat sixth in La Liga and appeared a team in decline, sorely missing forward Cristiano Ronaldo, who left for Juventus last summer.
Late Griezmann strike ends Atletico's away day hoodoo
Manchester United are optimistic ahead of a crucial period of fixtures as they are close to finding their best form, midfielder Ander Herrera said ahead of Sunday's top of the table showdown against Premier League leaders Manchester City.
Arsenal's young guns continued to shine as they dismantled Standard Liege 4-0 on a hectic night of Europa League action that produced a full house of Spanish victories on Thursday. A summary of the matches.
Liverpool have extended captain Jordan Henderson's contract, the Premier League side said on Tuesday, putting an end to speculation over his future at the Merseyside club.
Wounded VfL Wolfsburg, who drew 1-1 with Hanover 96 on Saturday after being crushed 5-1 by Bayern Munich last week, will meet Manchester United in Wednesday's Champions League game.
IMAGES from the UEFA Champions League last 16 first leg matches played across Europe on Tuesday
Arsenal manager Arsene Wenger is to stand down at the end of the season after a reign of almost 22 years that made him the most successful boss in the Premier League club's history.
Photos from the Champions League matches played across Europe on Tuesday
Images from the Champions League matches played on Wednesday
A summary of Wednesday's matches in the UEFA Champions League.
News of all that's transpired on and off the football field
Lionel Messi set a new Champions League scoring record with a hat-trick and Luis Suarez netted his first in Barcelona colours as the Spaniards comprehensively beat APOEL Nicosia 4-0 in the Champions League on Tuesday.
Schalke 04 beat rivals Borussia Dortmund 2-1 in the Bundesliga Ruhr valley derby on Saturday to confirm their improving form after a bad start to the season.
Tottenham Hotspur claimed a first victory at Chelsea for 28 years with Dele Alli scoring twice in the second half as they came back to win 3-1 and cement fourth place in the Premier League on Sunday.
Barcelona forward Lionel Messi equalled the Champions League scoring record of 71 goals when he struck for the second time in the 76th minute of Wednesday's Group F match at Ajax Amsterdam.
Here are five talking points from the weekend's action:
Champions League holders Real Madrid will face former European champions Liverpool, FC Basel and debutants Ludogorets of Bulgaria following the group stage draw on Thursday.
Manchester United and Manchester City must switch their focus from the Champions League to the Premier League when they meet at Old Trafford on Sunday in a derby that Louis van Gaal says will show whether United are true title contenders.
Manuel Pellegrini shrugged that he was "not worried about Chelsea" despite seeing his Manchester City team fall further behind the Premier League leaders at the end of a dispiriting week for both the Chilean and his champions.
Manchester City suffered a shock League Cup defeat at the hands of a reinvigorated Newcastle United, who reached the quarter-finals with a superb 2-0 away win on Wednesday that left the holders nursing the wounds of a bruising past eight days.
Bayern Munich defender Jerome Boateng returned to haunt his former club with a last-gasp goal that secured a 1-0 win over English title holders Manchester City in their opening Champions League Group E clash on Wednesday.
Real Madrid got their Champions League title defence off to a strong start on Wednesday by convincingly beating AS Roma 3-0 at home with goals from Isco, Gareth Bale and a stoppage-time strike from returning striker Mariano Diaz.
Ruthless Bayern Munich scored five goals in the first 35 minutes on the way to a 7-1 demolition of AS Roma on Tuesday which bore an uncanny resemblance to Germany's win over Brazil by the same score in the World Cup semi-final.
VfL Wolfsburg reached the Champions League last 16 and dealt a knockout blow to Manchester United with a 3-2 victory to claim top spot in Group B and condemn their opponents to the Europa League on Tuesday.
A summary of all the Champions League matches played across Europe on Tuesday
Carlos Tevez scored twice to give Serie A leaders Juventus a 3-2 win over Fiorentina on Wednesday but Lazio prevented them from celebrating the title by thumping bottom club Parma 4-0, which condemned their opponents to Serie B.
Leicester City added another tale of remarkable success to an incredible year by reaching the last 16 of the Champions League in their debut season with a 2-1 victory over Club Bruges.
Cristiano Ronaldo set a record for goals scored in the group stage of the Champions League of 11 when he netted four against Malmo in Group A on Tuesday.
Chelsea face the prospect of having veteran Didier Drogba as their only fit striker for their visit to Manchester United on Sunday in what is usually one of the standout matches of the Premier League season.
The three teams with 100 percent records in this season's Champions League can secure their places in the knockout stage this week with two games to spare.
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