Barcelona beat Manchester City 3-0 in Monza on Wednesday to put one foot in the Champions League semifinals.
Asisat Oshoala opened the scoring in the first half and then won a second-half penalty, which was converted by Mariona Caldentey.
City spurned the chance to score an away goal when Chloe Kelly's spot-kick was saved by Sandra Panos before Jenni Hermoso completed the scoring for Barca late on.
The game was played in Italy due to travel restrictions on flights into Spain from England, but City will benefit from home advantage when they attempt to turn the tie around in Manchester next week.
Barca and City have both invested heavily in their women's teams in recent years. Domestic honours have followed, but European success has so far eluded them. The Blaugrana, who have won all 20 of their league games this season, were runners-up in 2019 and beaten semifinalists last year, while City made the last four in 2017 and 2018.
Barca started strongly at the U-Power Stadium and City were indebted to goalkeeper Ellie Roebuck, who made impressive saves from Oshoala, Aitana Bonmati and Alexia Putellas.
However, she couldn't keep out Oshoala's smart finish from 18-yards just before half-time and the tie drifted away from City when Mariona scored from the spot after Demi Stokes had fouled Oshoala.
City had an immediate chance to get back in the game but Panos saved Kelly's penalty after Maria Leon had brought down Lauren Hemp.
Gareth Taylor's side pushed for an away goal, with Sam Mewis coming close, but they were hit on the break late on when substitute Hermoso turned home after Putellas had hit the post.