The Arsenal forward needed only a few seconds on the pitch to get off the mark following her introduction just after the hour mark with an acrobatic hooked finish and would add two more to her tally in a second-half turnaround.
Another substitute, Bethany England, scored the Lionesses’ second, with a touch on the line to ensure the ball went into the back of the net.
Mead then scored at the back post before tapping the ball into an empty net in the 78th minute to bring up her hat-trick.
It was the first competitive fixture for the Lionesses at England’s national stadium since Wembley reopened in 2007, but it was viewed by a disappointing 23,225, significantly lower than the 30,000 the Football Association had been expecting for the fixture.
However, the result ensures England remain top of the group, with their lowest number of goals of the campaign so far after thrashing North Macedonia 8-0 and knocking 10 past Luxembourg as they brought Northern Ireland’s eight-game winning run in competitive fixtures to an end.
England dominated the early period and had multiple shots blocked while Northern Ireland struggled to get out of their half.
Ellen White had an opportunity to close the gap to Kelly Smith’s international goal record when a clearance from goalkeeper Burns was straight at the number nine, but her shot lacked direction and was easily parried behind by the goalkeeper.
Lauren Hemp hit the crossbar after cutting in from the left wing and defender Alex Greenwood also had a strike from range hit the woodwork but Northern Ireland kept their shape in defence and made it difficult for the home side.
The visitors defended resolutely to ensure the game stayed level at the break despite 17 shots from England.
With almost their first opportunity of the match, early in the second half, Northern Ireland looked to threaten when a break down the left almost found Caragh Hamilton at the far post but Greenwood got a slight but vital touch to prevent her from turning it on target.
England grew increasingly desperate in search of a way to break the deadlock, even moving to a back two for a time, with all the other players attacking.
However, just moments after coming on, it was Mead who finally broke the deadlock for England. A corner was palmed out by Burns and bounced around the box before the in-form Arsenal player turned and volleyed the ball into the back of the net.
England doubled their lead shortly afterwards, with the Northern Ireland defence starting to look slightly tired. Hemp’s cross-shot was heading in but Bethany England arrived at the far post to tap the ball in and deny Hemp a deserved first international goal.
The game had barely kicked off again when Mead had her second of the match. Hemp was the provider for a second time after shaking off the Northern Ireland defender to send a ball over the top for Mead to finish with another fine finish on the volley.
Mead then secured her hat-trick in the 78th minute. Bethany England was played in by Kirby and though Burns was out quickly to prevent her from reaching the ball, it fell to Mead who tapped the ball into the empty net to score her third goal in 14 minutes as England cruised to a 4-0 victory.
Additional reporting from PA