Stand-in manager Jason Tindall, deputising for Eddie Howe, who remains sidelined with pneumonia, masterminded another clinical performance to edge the Magpies closer to Champions League qualification.
The hosts wasted no time asserting dominance, with Jacob Murphy firing an early strike into the roof of the net from a tight angle, his third goal in as many matches.
Palace had a chance to respond when a VAR review awarded them a penalty after Nick Pope's collision with Chris Richards, but Eberechi Eze's tame spot-kick was comfortably saved by Pope.
The miss proved costly, as Marc Guehi inadvertently turned Harvey Barnes' cross into his own net, doubling Newcastle's lead.
Barnes then added a third with a fierce low drive, before Fabian Schar's glancing header from Murphy's free-kick made it 4-0 before half-time.
Alexander Isak capped the rout in the 58th minute, curling a precise effort into the bottom corner for his 25th goal of the season. Newcastle eased off in the second half, preserving energy for their upcoming clash with Aston Villa.
Tindall, who has overseen victories over Manchester United (4-1) and now Palace, played down suggestions that management was straightforward. "It's certainly not easy," he said with a smile. "But the lads have delivered two excellent performances in a few days, and I'm delighted with that."
He stressed the importance of allowing Howe to focus on recovery, adding, "The last thing Eddie needs is the stress of football. We've worked together for 17 years, so we know what's expected to deliver performances we pride ourselves on."
Palace manager Oliver Glasner offered a blunt assessment of his side's capitulation. "Everything went wrong," he said. "Credit to Newcastle for their pace, directness, and energy. We couldn't compete from the start."
The defeat, following a 5-2 loss to Manchester City, marks Palace's sixth failure to win in their last seven away games against Newcastle.
Recent updates from Newcastle confirm Howe remains in hospital but is responding well to treatment. A club statement on X expressed gratitude for fan support and optimism for Howe's return, stating, "Eddie's in good spirits, and we're all behind him."
Meanwhile, Tindall's seamless leadership has kept the Magpies flying high, with their sights firmly set on a top-four finish as they prepare to face Villa in a pivotal encounter.
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Arsenal have reportedly cooled their pursuit of Wolverhampton Wanderers' forward Matheus Cunha due to concerns over his on-pitch behaviour, according to recent reports.
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