Before the kick-off players stood at a distance from each other around the centre circle for a minute of silence in memory of the 27,000 victims of the pandemic in the country.
Lucas Ocampos gave Sevilla the lead from a 56th-minute penalty and the 25-year-old Argentine set up Fernando to add the second six minutes later.
The match dubbed 'El gran derbi' was played at an empty Estadio Ramon Sanchez Pizjuan because of the strict health protocols under which Spanish football has been allowed to return.
As part of the deal, players have to arrive wearing masks and gloves and their temperatures must be taken before entering the stadium. During the match the substitutes have to keep their masks on and sit at the approved distances in the rows behind their coaches.
Ocampos, who scored for a fifth consecutive game, celebrated his feats on his social media account.
✔️ictoria!!!! 😉 #ElGranDerbi #WeareSevilla pic.twitter.com/gqx2i2yBTJ
— Lucas Ocampos (@Locampos15) June 11, 2020
"The whole team was very good," Ocampos told the club website. "We were strong mentally by scoring first and knowing how to manage the match.
"Returning was so good but returning like that ... there's no words for it. Now we have to adapt and continue because there are 10 cup finals to go."
Champions League in sight
Following the victory, Sevilla remain third in the table and in the driving seat for one of the four berths that lead to next season's Uefa Champions League.
Real Madrid and Barcelona are above them. Their roster of superstars will get their first taste of competitive action since 10 March over the weekend.
On Saturday, pacesetters Barcelona travel to Mallorca who are in the relegation zone. On Sunday, Madrid host Eibar who are also fighting against the drop to division two.
"I always believed we would play again," said La Liga president Javier Tebas after Thursday night's game.
He hinted that some fans might be able to attend stadiums before the season finishes on 19 July.
La Liga is the third major European league to return from the coronavirus shutdown. The German Bundesliga resumed last month and Portugal's Primeira Liga relaunched on 4 June. England's Premier League is preparing for its comeback on 17 June.
France's Ligue 1 was declared over on 30 April following a government ban on professional sports.
Paris Saint-Germain were anointed champions while Amiens and Toulouse were relegated to Ligue 2. However those clubs took their case to the country's top court which ruled that their demotion was illegal.
