Dave Watson's side thrashed Brighton & Hove Albion 5-0 last month to set up the clash against the Eagles, who beat Mansfield Town on penalties in the third round.
United will travel to Selhurst Park on Friday, 19th January 2018 for a 7pm (UK time) kick-off.
Kelland Watts hit a hat-trick in the last round, with Lewis Cass and Kurtis Russell also on target for the young Magpies.
Newcastle reached the quarter-final stage last season before losing 5-3 to Tottenham Hotspur.