Robert Lewandowski got off the mark for Barcelona with a double as Ansu Fati starred as a substitute in a 4-1 victory over Real Sociedad on Sunday, while Villarreal won at Atletico Madrid.
Poland striker Lewandowski, celebrating his 34th birthday, put Barca ahead inside 50 seconds before Alexander Isak levelled for La Real in San Sebastian.
But Fati came off the bench to create goals for Ousmane Dembele and Lewandowski, before completing the scoring himself.
Barca’s first win of the season followed a disappointing goalless draw at home with Rayo Vallecano on the opening weekend.
Earlier, Villarreal moved to the top of the fledgling table as second-half goals from Yeremy Pino and Gerard Moreno secured a 2-0 victory at Atletico.
Unai Emery’s men opened their season with an impressive 3-0 win at Real Valladolid last weekend, but the scalp of Atletico will raise hopes of a possible challenge for Champions League qualification.
The away side made a fast start at the Estadio Metropolitano, with Atletico goalkeeper Jan Oblak forced into fine saves from Giovani Lo Celso and Etienne Capoue.
Moreno thought he had given Villarreal a half-time lead, but his effort was ruled out for a handball.
Matheus Cunha was introduced midway through the second period by home coach Diego Simeone in place of Alvaro Morata and almost broke the deadlock in the 72nd minute, only to be denied by keeper Geronimo Rulli.
Teenage winger Pino instead put Villarreal in front just a minute later, capitalising on a poor clearance to fire a fine low shot into the bottom corner.
Atletico’s Nahuel Molina was sent off deep into injury time and Moreno netted in the 97th minute to send Villarreal top.