The Spaniards were given an early opportunity to take the lead after being awarded a penalty in the 12th minute.
Alvaro Morata stepped up but once again failed to convert as his goal drought continues.
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Despite this, the hosts did eventually break the deadlock courtesy of an outlandish own goal from Newcastle goalkeeper, Martin Dubravka.
Spain's Pablo Sarabia produced a fine strike from distance which rattled the crossbar and fired the ball high into the air.
As the ball descended, Dubravka looked to parry it over the bar. Instead, he pushed into the back of his own net to give Spain a 1-0 lead in Seville.
From that point on, things quickly deteriorated for the Slovaks.
Aymeric Laporte bagged a second for Spain just before the half-time whistle.
In the second-half, Sarabia and Ferran Torres added two more efforts as the hosts moved 4-0 ahead.
Juraj Kucka put the ball in the back of his own net to further worsen Slovakia's position.
In the end, Spain celebrated a crushing 5-0 victory which will undoubtedly lift confidence following a stuttering start to the tournament.
Read the full report on our sister site, Football365.
Sweden leave it late
Over in Saint Petersburg, Sweden got off to a flyer against Poland with Emil Forsberg opening the scoring in the 2nd minute of the game.
Forsberg was back on the scoresheet in the 59th minute as Sweden doubled their advantage.
Robert Lewandowski - who hit the bar twice in the first-half - produced a wonderful long-range effort to put his side back in contention.
Poland needed a win to stand any chance of qualifying. However, their hopes began to fade when Jakub Swierczok's goal was disallowed for offside.
Time was running out but with five-minutes remaining, Lewandowski scored his second of the night to set up a dramatic finish.
There was no fairytale ending for the Poles though as Viktor Claesson scored the winning goal for Sweden in added time.
Read the full report on our sister site, Football365.
Stat of the day
From OptaJoe: "Today is the first time two EUROs matches have seen 5+ goals on the same day (Sweden 3-2 Poland, Spain 5-0 Slovakia) since 21st June 2000 (Spain 4-3 Yugoslavia, Netherlands 3-2 France)."
What's next
Having won the group, Sweden will now take on one of the third-placed teams. Their opponents will be confirmed following the conclusion of tonight's final group stage games.
That clash will take place on Tuesday at Hampden Park.
After bagging a second-placed finish, Spain will face the runners-up of Group D, Croatia.
Since losing their Euro 2020 opener to England, the Croats have grown from strength to strength. A 1-1 draw with the Czech Republic was followed by a 3-1 thumping of Scotland.
Slovakia finished third in the group and could face Belgium in the next stage of the tournament. Their fate will be determined following the conclusion of tonight's final Group F games.
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