Two switches to the side beaten by Chelsea saw Georgia Brougham and the injured Molly Pike make way for captain Sophie Barker and midfielder Missy Goodwin, who was making her first start for the Foxes.
Ashleigh Plumptre recovered in time for her to take a place in the back line, which was switched to a four-at-the-back system, but the defence was breached inside two minutes.
Caitlin Foord’s cross from the left was flicked home by England forward Beth Mead to hand the title-chasing Gunners a perfect start.
Jonas Eidevall’s side kept up the pressure on Leicester’s goal when Mead’s free-kick deflected off Shannon O’Brien to send it wide.
Miedema soon took McCabe’s cross in her stride and fired in a powerful left-footed strike that Lambourne did well to flick away with her legs, ahead of Plumptre blocking Mead’s follow-up.
Further chances followed via Foord, again denied by Lambourne, who stood firm once more as Katie McCabe crossed to Miedema, with the shot-stopper producing a fingertip save to send it onto the post.
The hosts did create an opportunity when free-flowing football from the Foxes led to O'Brien crossing for Natasha Flint and her first-time effort being turned wide by full-back Laura Wienroither, who was in the right place at the right time.
Back at the other end, Arsenal captain Kim Little drove through the middle of midfield before picking out Foord, who was again unable to beat Lambourne at her near post.
It was more of the same from the north London outfit early in the second half. Mead's fierce strike looked destined for the top corner until Esmee De Graaf got back to superbly head off the line.
The Leicester resistance since the opener was broken on 67 minutes. Miedema had the simple task of slotting into an empty net after Jemma Purfield flicked the ball back into her path following a one-two with Mead.
Paige Bailey-Gayle, introduced with 20 minutes remaining for Flint, looked to add some pace to the attack, but had little support to fashion an opportunity, despite O'Brien's willing running across the midfield.
And the visitors’ third goal arrived with a quarter of an hour to play. De Graaf was unfortunate to get the final touch that took the ball past Lambourne, sliding in to try and prevent Miedema finishing off a neat Arsenal move herself.
Four minutes later, it was four, and a second own goal, when substitute Nikita Parris’ cross was turned home by Plumptre.
The fifth came shortly after and it was another Arsenal substitute who rounded off the scoring. Parris played a quick one-two with Mead, crossing for USA international Tobin Heath to tap in at the back post with eight minutes remaining.
Demi Lambourne made some smart saves during the first half.
The scoreline was ultimately harsh on Leicester, who recovered from an early setback to hold their own for the majority of the contest, but conceded several late goals as Arsenal set their sights on returning to the division's summit.
Where do we stand?
The midfielder was making her full debut for the Foxes.
City remain 11th in the table, on 12 points from 19 games in their debut Barclays FA Women’s Super League season.
City now have three games remaining this campaign.
After a two-week break from competitive action, Leicester return to league action on Sunday 24 April, travelling to face Manchester City at Academy Stadium (2pm BST kick-off).
City: Lambourne, De Graaf, Howard, Plumptre, Purfield; Goodwin, Tierney, Barker, Gregory; O’Brien, Flint (Bailey-Gayle 71’).
Subs not used: Harris, Brougham, Smith, Robinson, Boddy, Devlin, Baker.
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