The goalless draw does no favours for Rafael Benitez's men in their battle to beat the drop, with the Magpies still only a one-point off the bottom three.
Benitez made seven changes to the starting XI that were beaten 1-0 by Premier League leaders Manchester City on Wednesday.
Encouraging start by Magpies
It was two of Benitez's introductions who carved out the hosts' first excitement of the half as Dwight Gayle just lacked the height to convincingly meet Isaac Hayden's cross.
Under ten minutes later, a pin-point ball from Mikel Merino found Gayle, and the striker's shot at the by-line almost allowed Joselu to capitalise on Matt Ryan's spill in the Seagulls' goal.
But the visitors' threat was evident as they dictated the possession after the Magpies started brightly.
Nervy moments for Newcastle
After Anthony Knockaert registered Brighton's first shot on target on 26 minutes with an attempt straight at Karl Darlow, two nervy moments quickly followed for the home crowd.
Glenn Murray was picked out unmarked at the back post but was deemed offside, before a corner kick eventually fell to Shane Duffy, but the Irishman squandered the chance with a close-range shot as it steered into the middle of the Gallowgate End.
The Seagulls defensive stubbornness meant Newcastle could only threaten from long distance with Joselu, the next to try his luck with a low drive, before Dale Stephens' header landed inches away from nestling into the top corner.
Same story on resumption
Similar to the first period, Newcastle began in lively fashion, with only the brilliance of Ryan denying the home side the lead in the 49th minute.
Matt Ritchie's corner made its way out to Hayden, and just as it looked his deflected effort had pushed United in front, he stunningly reached the shot with an outstretched right-hand.
And from the following corner, another opportunity was witnessed as Jamaal Lascelles glanced his header just wide of the left-hand post.
On the hour-mark, Ryan again proved defiant with a save just as good as his first to stop Gayle from converting Christian Atsu's cushioned delivery.
Brighton's response was kick-started on 54 minutes when Pascal Gross required a save from Darlow as he curled his free-kick around the wall.
And the Seagulls, who were a threat from corners all afternoon through Lewis Dunk and Duffy combined to force Darlow into excellent save.
If there were a period to highlight Newcastle's deep relegation struggles, Brighton's bossing of possession for the majority of the second-half - and the match - was it.
Like in midweek, St James' Park witnessed a late flourish, though albeit, lacked the winning goal that each supporter prayed for as the closest they seen to an equaliser fell through Atsu's aimless shot on 88 minutes.