Saturday's League Cup final was the start of a 12-day showdown between these two sides and it was clear both managers had learned from it.
The first half was a stalemate with the rivals largely cancelling each other out and momentum swung throughout.
Chelsea striker Mayra Ramirez and City defender Laia Aleixandri were locked in a physical battle, while Blues forward Aggie Beever-Jones showed her defensive nous, tracking back and minimising the home side's threat.
With key forwards Khadija Shaw and Aoba Fujino missing through injury, City interim boss Cushing turned to 19-year-old Lily Murphy and January signing Kerolin for attacking impetus, with the pair showing flashes of quality down the wings.
It was Kerolin who came to the fore in the second half, driving at Chelsea's backline and getting in behind on several occasions and playing a major part in the opener. Her cross picked out Aleixandri and, while Hampton pushed the Spaniard's header on to the bar, Miedema pounced to finish the rebound.
Miedema continued to test Chelsea captain Millie Bright, while Ramirez struggled to have the same impact at the other end, although she did have a goal ruled out for offside.
City forward Miedema's impact was significant as she not only provided the goals, but the ruthlessness which City badly missed in Saturday's cup final defeat.
All-in-all, it was a flat performance from Chelsea and they will need to offer more when City travel to London having claimed the upper hand in this hard-fought European tie.
The teams will meet for a third game in a row on Sunday in the Women's Super League, before next week's second leg, but it is clear Chelsea's quest for a quadruple will not be achieved easily.
Their 28-game unbeaten run under Bompastor comes to an end – but Chelsea have so often found a way to win and will still fancy their chances at Stamford Bridge, with Barcelona or Wolfsburg awaiting in the semi-finals.