At a time when the Magpies are unbeaten in the Premier League, Tranmere find themselves down in 17th position in League Two.
Match preview
Such was the level of Newcastle's performance against Manchester City on Sunday that Eddie Howe probably felt disappointed that his side never converted a 3-1 lead into maximum points.
However, a 3-3 draw at home to the defending Premier League champions and big favourites to win the title yet again will eventually be regarded as a point gained by the Magpies.
Goalkeeper Nick Pope had to produce numerous high-level saves to restrict City to just the three strikes, and the England international has undoubtedly been one of the signings of the summer thus far.
Although Newcastle arguably require one or two more high-profile names to help lift the club up the standings, everything continues to trend on an upward trajectory at St James' Park.
With a trip to Wolverhampton Wanderers to come at the weekend, this game will likely see the fringe members of the squad get an opportunity, but they will be motivated to retain their spots in Howe's plans going forward.
From Tranmere's perspective, they will welcome the opportunity to face a side of Newcastle's size, bringing in a capacity crowd and television revenue to boot.
Micky Mellon will be realistic about his team's chances of overcoming opponents who will have their eyes on winning this competition, but Tranmere have not performed as badly as their league position suggests.
Each of their three defeats this campaign have come by one-goal margins, two of those setbacks being against teams who occupy second and eighth spot in the table.
Goals remain an issue, though, with three of their five league goals in five games coming in the same match, and Mellon will be eager for his players to rise to the occasion at Prenton Park.
Tranmere Rovers EFL Cup form:
Tranmere Rovers form (all competitions):
Newcastle United form (all competitions):
Team News
Callum Wilson will not be risked by Newcastle after suffering a minor hamstring issue against Man City, while Dan Burn may also miss out after being kicked in the face with the ball towards the end of that fixture, resulting in his substitution.
Unless Matty Longstaff features before going back out on loan, Joe Willock may be the only player to retain his spot from the weekend.
Academy graduate Elliot Anderson will hope to be given an opportunity after making an impression during pre-season.
Lee O'Connor and Jon Nolan both come into contention for Tranmere with the midfield duo being introduced as second-half substitutes at the weekend.
Second-choice goalkeeper Mateusz Hewelt may also get a runout after playing in the previous round.
Tranmere Rovers possible starting lineup:
Hewelt; Byrne, Turnbull, Jameson, Dacres-Cogley, Nolan, O'Connor, Merrie, Bristow; Hemmings, Nevitt
Newcastle United possible starting lineup:
Dubravka; Krafth, Lascelles, Fernandez, Ritchie; S.Longstaff, Willock; Murphy, Anderson, Fraser; Wood
We say: Tranmere Rovers 1-4 Newcastle United
Tranmere will naturally take encouragement from Howe almost certainly making widespread changes to his starting lineup. Nevertheless, this is a united Newcastle group who will want to impress, and we are backing the Magpies to run away with this game.