The Ukraine international has struggled to find his feet for the Blues since arriving from Shakhtar Donetsk for £88m in January.
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But he is finally off the mark with a fizzing second half volley to make it two wins from two for new boss Pochettino in the United States.
Danny Welbeck had given Brighton the lead early on before £52m new-boy Christopher Nkunku levelled with his second goal of the tour.
A rash second yellow card for Seagulls defender Jan Paul van Hecke on the hour mark then opened the floodgates for the West Londoners, in front of over 65,000 fans in Philadelphia.
Mudryk volleyed a powerful effort in from 18 yards, Conor Gallagher grabbed a third and Nicolas Jackson raced through on goal to add a fourth – also his first for Chelsea after his £32m move from Villarreal.
Brighton got one back via a Joao Pedro penalty after Levi Colwill – against his old club – brought the ex-Watford striker down before Deniz Undav scored an injury time third.
Poch hinted pre-match that he would be willing to sacrifice these games and play the kids in order to ensure his senior stars come away unscathed for their August 12 Prem opener.
However, the Argentine decided to partially scrap that idea and sent out a strong-looking starting XI at the Lincoln Financial Field Stadium.
Kepa Arrizabalaga, Raheem Sterling, Ben Chilwell and Gallagher came in from the off having all come off the bench last week against Wrexham.
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Thiago Silva made his first appearance of the tour. Nkunku led the line in his first start for the club since his £52m move from RB Leipzig.
Ian Maatsen and Andrey Santos earned successive starts after impressive displays in the 5-0 win in North Carolina.
Colwill started at centre back against the club who had him on loan last season and the manager Roberto De Zerbi who wants him back.
Enzo Fernandez and Mykhailo Mudryk returned to the bench.
There was no Moises Caicedo in the Brighton squad having joined up with the team late. De Zerbi said this week the Ecuadorian will not leave if Chelsea do not increase their offer to meet the club’s evaluation of £100m.
Most of the early good work from Chelsea came down the left via Chilwell’s bursting runs forward while Sterling produced the first shot on target.
But it was Brighton who were rewarded – former Blue Billy Gimour’s cross towards the far post was flicked back by Kaoru Mitoma and Welbeck fired in off the bar.
The Seagulls were dominating as Chelsea tried and struggled to play out from the back. Welbeck almost grabbed an identical second from an Adam Lallana delivery.
Yet Chelsea responded well. Carney Chukwuemeka’s one-two with Maatsen on the edge of the box was deflected into the path of Nkunku who poked past Jason Steele.
Poch’s men continued to push, Maatsen somehow fluffing his lines from a Sterling pick-out as he attempted to grab his third goal of the tour.
At the break, Poch made four changes. Mudryk made his long-awaited arrival in the States alongside Marc Cucurella, Trevoh Chalobah and Cesare Casadei.
The second half was frantic. Brighton sub and summer signing Joao Pedro almost pulled off a beauty of a goal down the byline before Sterling wasted a glorious chance on the break.
And then, more drama as Brighton defender Jan Paul van Hecke was sent off for a second booking after a nasty collision with Casadei.
Poch rang the subs, and then a few minutes later, Chelsea produced their best move of the match to take the lead.
Mudryk combined beautifully with Jackson – who had just come onto the pitch – before volleying into the bottom corner.
Enzo Fernandez and Angelo had also been subbed on, as Gallagher and Jackson added the extras late on.