The defending champions have a lead to take back to Camp Nou while Lyon also triumphed in their first leg against APOEL Nicosia.
Lionel Messi shines for Barcelona in Champions League triumph
Two goals by Alexis Sanchez - his first in the Champions League - led Barcelona to a 3-1 first-leg win at Bayer Leverkusen on Tuesday to put the holders in the driving seat in theirlast 16 tie.
Barca, who are now unbeaten in 13 Champions League games and have scored in 28 consecutive matches in the competition, are trying to lift the trophy for the third time in four years.
While Chile forward Alexis struck twice, it was Lionel Messi who once again stole the show with another sublime exhibition of ball skills capped by a late third goal from the World Player of the Year.
"We are very satisfied with the result because scoring three goals away is very important," said Barca coach Pep Guardiola.
The visitors grabbed the lead in the 41st minute after a brilliant left-footed flick by Messi sent Alexis racing through on goal.
Michal Kadlec equalised in the 52nd minute but the 23-year-old Chilean made it 2-1 three minutes later.
Messi completed the win, starting an 88th-minute move that also involved Dani Alves and finishing it with a volley at the far post as Barca avenged their 2001 defeat by Leverkusen, the last German club to beat them.
Asked whether he was planning to rest Messi, who has now scored a remarkable 25 goals in his last 24 Champions League matches, Guardiola replied: "Why? People want to see players like him.
"His life is football. He doesn't care. He's just happy when he plays. For us it's very important when he plays."
Meanwhile, Lyon laboured against a resolute APOEL Nicosia before a second-half goal from Alexandre Lacazette earned them a 1-0 home win in their first leg.
France Under-21 striker Lacazette netted his maiden Champions League goal in the 58th minute thanks partly to a deflection as Lyon gained a victory they just about deserved.
Lyon, who will travel to Cyprus for the second leg on march 7, could have gone ahead early on but were denied a possible penalty in the third minute after Ederson appeared to have been brought down by goalkeeper Dionisios Chiotis in the box.
APOEL, who qualified for the last 16 by topping a group featuring Zenit St Petersburg, Shakhtar Donetsk and Porto, had little to show for themselves offensively throughout as they waited for the perfect counter-attack that never materialised.
The hosts piled on the pressure in the first half but APOEL, the first Cypriot side to reach this stage of the competition, held on thanks to their stout defence.
The second half started like the first one ended, with Lyon - who only made the last 16 for the ninth straight time after a 7-1 thrashing of Dinamo Zagreb - pushing hard for the opener.
Ederson dribbled past Chiotis, slotted the ball towards the empty net only for Paulo Jorge to clear off his line.
Lacazette finally broke the deadlock when his curled shot took a deflection off an APOEL defender into the far top corner.
Jimmy Briand, who replaced Lacazette right after his goal, sent over a perfect cross but Ederson's header went just wide as Lyon missed out a golden opportunity to double the tally.