Reigning European Champions Chelsea cruised to a 2-0 victory over French title holder Lille Tuesday, while the Juventus-Villarreal tie ended in a 1-1 draw after Dusan Vlahovic had a dream in a Champions League debut.
Germany's Kai Havertz headed home eight minutes into the game which saw Chelsea striker Romelu Lukaku benched. American Christian Pulisic got the second to leave the Blues in control of the tie.
In Villarreal, Serbia international Vlahovic scored 31 seconds into his debut, according to UEFA, after an 80 million euros ($91 million) move to Juve from Fiorentina in January. But Dani Parejo leveled in the 66th for the Europa League champion from Spain.
The return legs in Lille and Turin are on March 16.
Havertz, who scored the winner in last year's Champions League final against Manchester City and in the Club World Cup final against Palmeiras 10 days ago, was a threat from the outset at Stamford Bridge.
He missed two good opportunities but then came third-time lucky in the eighth minute when he headed home Hakim Ziyech's corner kick.
Havertz almost got a second in the 59th but Pulisic then did better four minutes later when he chipped over Lille goalkeeper Leo Jardim off N'Golo Kante.
Lukaku, who had a modest showing in the weekend league win at Crystal Palace, did not play, with manager Thomas Tuchel stating fatigue.
"We have a lot of good strikers so it’s good to have a change and not make it easy for our opponent," Havertz insisted.
"We didn’t play our best and it was hard. We could not get our usual aggressiveness but we won 2-0. We have a lot of chances to win another trophy."
Juventus held
Juve meanwhile had a dream start into its first-ever meeting with Villarreal when Vlahovic controlled a long ball from defender Danilo and between two defenders found the bottom left corner a mere 31 seconds into the game.
"It was huge to score on my debut; it was very emotional," Vlahovic said. "However, I cannot be 100% satisfied because we have not won the game. We have to keep working hard."
StatsPerform said Vlahovic became only the third player to score inside the opening minute of his first Champions League start, joining Andreas Moller of Borussia Dortmund 1995 against Juventus and Ishak Belfodil of Hoffenheim against Manchester City in 2018.
Villarreal's Giovani lo Celso hit the left outside post in the 13th but the hosts got the equalizer in the 66th when the unmarked Parejo drove on a chipped ball from Etienne Capoue.