Rodríguez Jiménez (Dismissed at67'minutes)
Goals from Marco Asensio and Nacho gave Carlo Ancelotti's side an early lead, but Granada's Luis Suarez pulled a goal back just before half-time.
Winger Vinicius Junior restored Los Blancos' two-goal advantage shortly after the restart with Monchu then sent off for the hosts in the 67th minute.
Ferland Mendy wrapped up the win for the visitors, adding a fourth after 76 minutes.
The win meant Real Madrid climbed above Sevilla and Real Sociedad to the summit of La Liga.
Meanwhile, strugglers Granada dropped into the bottom three on goal difference.
Vinícius Júnior (56'minutes),
Kroos (19'minutes, 25'minutes),
Real Madrid reached the Champions League knockout stage for the 25th successive year with a comfortable win against Sheriff Tiraspol in Moldova.
David Alaba opened the scoring with a free-kick that deflected beyond goalkeeper Giorgos Athanasiadis.
Toni Kroos added a second before the break, firing in off the crossbar, while Karim Benzema then made it three.
It means Real Madrid are through with a game to spare, as are Inter Milan, who beat Shakhtar Donetsk earlier.
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Manchester City came back from behind to beat Paris St-Germain and secure qualification for the Champions League last 16 - doing so as Group A winners.
City's outstanding display reaped the reward it deserved, as they showed character as well as class after Kylian Mbappe swept PSG into a 50th-minute lead.
PSG manager Mauricio Pochettino, heavily linked with Manchester United following Ole Gunnar Solskjaer's sacking, was left disappointed as City hit back in style to turn the game around.
New Barcelona manager Xavi celebrated his first game in charge at the Nou Camp with a slim derby victory over Espanyol in La Liga.
Although the home fans were able to claim bragging rights over their city rivals, the visitors could easily have won the game having wasted numerous chances in the second half.
Xavi eventually saw his side take the lead seconds after the restart through a Memphis Depay penalty.
The win puts Barca sixth in the table.
Vinicius Junior scored two goals, including a brilliant solo effort, as Real Madrid thrashed Shakhtar Donetsk in the Champions League.
An own goal by Sergiy Kryvtsov, who turned in a Lucas Vazquez cross, gave Real a one-goal lead at the break.
Vinicius scored twice in five minutes after the restart, sweeping in from close range before beating three players to add a brilliant third.
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Real Madrid returned to the top of La Liga with a hard-earned victory over Rayo Vallecano at the Bernabeu.
Toni Kroos put the hosts ahead after 14 minutes with a well-taken, side-footed finish from Vinicius Junior's pass.
Karim Benzema doubled the advantage before half-time, slotting in his 10th league goal of the season from David Alaba's cross.
Substitute Radamel Falcao headed in with 13 minutes left but Rayo could not find an equaliser and remain sixth.
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