Substitute Vivianne Miedema scored a brace as Manchester City inflicted Chelsea’s first defeat of the season by beating them 2-0 in their Champions League quarter-final first leg at the Joie Stadium.

Miedema, having come off the bench for the start of the second half, put City in front on the hour mark, rifling in the rebound when Hannah Hampton tipped Laia Aleixandri’s header against the crossbar.

And after Chelsea substitute Johanna Rytting Kaneryd had struck the bar at the other end in the 80th minute, Miedema added her second with two minutes of normal time remaining to give City a two-goal advantage heading into next Thursday’s second leg at Stamford Bridge.

That match will complete a series of four successive meetings between the sides, which started with Chelsea’s 2-1 triumph on Saturday in the League Cup final at Pride Park that gave them their first trophy under boss Sonia Bompastor.

They have now suffered a maiden loss of the Frenchwoman’s tenure, ending an unbeaten run of 28 games since she took charge last summer – of which 26 were wins – and 31 matches in total.

City, meanwhile, have a first win of Nick Cushing’s interim tenure after he replaced Gareth Taylor ahead of the quartet of fixtures, which continues with Sunday’s Women’s Super League clash at the Etihad Stadium.

With Khadija Shaw and Aoba Fujino dropping out having come off with injuries in Saturday’s contest, Kerolin and 19-year-old Lily Murphy came into City’s starting attack, while Cushing also opted to replace Miedema with Jess Park.

Bompastor made two changes which included former City midfielder Keira Walsh returning to Chelsea’s line-up after three games out.

Cushing had spoken about Saturday’s result serving as “fuel” for his team, and City started brightly as Kerolin shot over and Jill Roord’s strike was gathered by Hampton.

Chelsea registered an attempt with Nathalie Bjorn’s header being saved by Ayaka Yamashita before Hampton was called upon again twice in quick succession just prior to the half-hour, dealing with efforts from Murphy and Mary Fowler.

A Chelsea burst forward soon after ended with Catarina Macario heading over from Lauren James’ cross, and the opening stages of the second half saw efforts from James and Roord saved.

City then broke the deadlock when Aleixandri sent a header goalwards from Fowler’s delivery, Hampton did well to divert it against the woodwork and Miedema, who had replaced Murphy at the break, was on hand to crack the loose ball home from close range.

After Miedema saw a further shot parried by Hampton, Chelsea had the ball in the net in the 71st minute as Mayra Ramirez slotted in, but the flag went up for offside.

The visitors continued to push for a leveller and Rytting Kaneryd’s shot came back off the bar and fellow substitute Weike Kaptein saw an effort parried by Yamashita, before Miedema struck again as stoppage time drew near, slotting into the corner having been fed by Kerolin.