Barca's 1-0 success against Atletico Madrid at Camp Nou headlined proceedings, with Lionel Messi netting the decisive goal in the 85th minute.
Atletico will by no means feel out of the tie, though, and proved they can soak up Barcelona pressure ahead of next week's second leg.
Barca completed a dazzling 3-1 win in La Liga over Atletico 10 days ago but, on their return to Camp Nou, Diego Simeone's reigning Spanish champions turned in a performance recalling memories of the organisation and intensity that saw them avoid defeat over six games against the Catalan club last season.
Luis Suarez spurned a glorious chance to break the deadlock nine minutes before half-time as a fixture responsible for numerous memorable moments over recent seasons failed to fully come to life.
Despite tightening their usual grip on possession as the match progressed, Barcelona were frustrated by a staunch Atletico backline until Sergio Busquets went down under minimal contact from Juanfran when a Messi free-kick was partially cleared.
Visiting goalkeeper Jan Oblak superbly got a firm hand to the Argentinian's 85th-minute spot-kick, but he was helpless to prevent Messi from netting the rebound.
Villarreal also scored the only goal of their match five minutes from time, with Bruno's late effort giving them a 1-0 home win against Getafe.
Wednesday's other quarter-final first leg saw Malaga and Athletic Bilbao play out a goalless draw.
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