Zinedine Zidane's side returned to domestic action after claiming victory over Atletico Madrid on penalties to take the Spanish Super Cup in Saudi Arabia on Sunday.
Subsequently fielding a slightly diminished squad, with Eden Hazard, Gareth Bale and Sergio Ramos all absent, Los Blancos nevertheless extended their unbeaten league run to 11 games and rose three points clear of Barcelona, who play Granada on Sunday.
A proactive Sevilla took control of the early proceedings, dominating possession and allowing Real just a handful of opportunities to involve themselves in the game.
A defensive lapse from the 33-time La Liga champions nearly saw them fall behind after just 12 minutes as a slack Casemiro pass was seized upon by Sevilla's Munir.
The resulting effort fell short but served to jolt a passive Madrid into action, led by Luka Modric. The Croatia midfielder launched a challenge down the centre of the pitch, sidestepping the Sevilla defence and finding Luka Jovic before the latter's pass was intercepted and the threat fizzled out.
Casemiro then made a bid to atone for his earlier slip by firing a powerful shot at Tomas Vaclik, the long-distance strike just curving high of the target as Madrid were denied an opener.
Sevilla looked to have broken the deadlock instead just three minutes later as Luuk De Jong captialised on a corner to head home the opening goal of the contest. VAR ruled that defender Eder Militao was blocked by Nemanja Gudelj as he pursued the goalbound ball, however, and the effort was disallowed.
Julen Lopetegui's side recreated their positive start to the first half upon the resumption after half-time, but it was Madrid who found the breakthrough.
After a neat passage of play with Jovic, Casemiro was ideally placed to fire the ball past Vaclik and hand his side the advantage in the 58th minute.
Sevilla were quick to reply, with Munir battling forward minutes later to find De Jong, fired a left-footed shot from the edge of the box past Courtois and into the right-hand corner of the goal.
Parity did not last long, however, as Casemiro then rose to connect with a Lucas Vazquez cross and headed the ball beyond a helpless Vaclik.
A hat-trick looked possible for the Brazilian when he collected the ball on the edge of the box five minutes later, but his shot rolled marginally wide.
Modric then attempted to put the game to bed, launching a long-range effort from outside the penalty area which flew just wide of the target.
Sevilla had a late chance but substitute Youssef En-Nesyri shot was wide and the hosts took all three points, with their opponents remaining fourth in the table.