Separated by a distance of only 40 miles, these two sides are close in more ways than one, with the visiting Spireites flying high atop the National League and the Ammies entrenched in the middle of League Two, marking just 13 league places between them.
The stakes are sky-high, thanks to the winner progressing to join the 44 Premier League and Championship clubs in the hat for the third round.
With the match being broadcast across the nation on Sunday afternoon, Planet Sport brings you all you need to know ahead of the big game.
When, where and how to watch
When: Sunday, December 5, 17.15 GMT
Where: Peninsula Stadium, Salford
How to watch: ITV4, live from 16.30 GMT
Best bets for Salford City vs Chesterfield
Both sides coming into the game in good form
We're set for a high-quality clash in Greater Manchester, with both sides coming into the encounter in a rich vein of form.
Hosts Salford are unbeaten in six matches in all competitions, rising from 19th in League Two at the end of October, to 11th.
Gary Bowyer's men comfortably saw off struggling Oldham Athletic 2-0 last weekend and earned a dramatic 1-1 draw four days earlier against Bristol Rovers with a 95th-minute equaliser, despite being down to nine men.
However, even that pales in comparison to the trail left by the Chesterfield juggernaut. The visitors are top of the National League having lost just once all season - which was all the way back in September - and are currently on a ten-match unbeaten run in all competitions.
The Derbyshire outfit's last game came on the same day Salford were earning themselves that drama-laden draw with Rovers, when they were stunningly held to their own 2-2 draw at home to Altrincham, who scored in the 84th and 96th minutes. However, they had comfortably picked up three points before that, seeing off Solihull Moors 2-0 away from home.
Earlier cup exploits
Thanks to their status as members of England's fifth tier, Chesterfield entered the FA Cup a stage earlier than Salford, but made light work of a trip to National League North side Curzon Ashton, recording a 4-0 victory thanks to goals from Jeff King, Nathan Tyson and Liam Mandeville, plus a penalty from Stefan Payne.
Their reward was an assignment to host fellow National League side Southend United and the Shrimpers also found themselves dispatched. Despite going a goal behind inside four minutes, strikes from Saidou Khan, Luke Croll and Kabonga Tshimanga handed Chesterfield a 3-1 win, as both sides ended the game with ten men.
Salford, meanwhile, have played just once in this season's competition, keeping a clean sheet away from home as they defeated Dagenham & Redbridge 1-0 last month. A third-minute header from Jordan Turnbull proved to be just enough for the Ammies to knock out their National League hosts.
We meet again
Salford's relatively short history above the lower trappings of non-league has led to these two meeting only twice in the past, as their paths crossed for just one season, in the 2018/19 National League.
Both sides won their respective home match on the pair of occasions they met that term, with Salford drawing first blood thanks to a 3-2 victory.
Danny Whitehead's 89th-minute winner gave the Ammies three points in a topsy-turvy game that had seen Chesterfield twice go behind before coming back to equalise.
The Spireites did have their revenge in the reverse fixture back in Derbyshire, however, as Alex Kiwomya's brace made sure of a 2-0 win, handing Salford their first loss in 21 matches.
Chesterfield would go on to finish 14th. However, it was a season of glory for Salford, who, in their only season in the National League, earned promotion to League Two through the play-offs.
Immovable object hit by irresistible force
Salford have been perfectly solid at the back, and have the sixth-best defence in League Two, with 19 goals conceded.
Yet, that back four is likely to face one of its biggest tests yet when it comes up against a sparkling Chesterfield attack, who have ripped several teams apart on their way to racking up 35 National League goals in 17 games.
The hosts' defence kept a clean sheet against Oldham in their most recent outing and have conceded just twice in their last five. However, the last time the Spireites failed to score was all the way back in mid-September.
In addition, James Rowe's men have scored at least twice in their last five consecutive games, hitting four against Weymouth in their November zenith.
Perhaps we'll finally get an answer to that favoured question of theoretical physics - what would actually happen if an immovable object was hit by an irresistible force?
Goalscorer bets for Salford vs Chesterfield
There is one immediate attention-grabber when it comes to which individual players are likely to find the back of the net in this one, and in keeping with their form, the man in question is a Spireite.
Kabongo Tshimanga has been in scintillating form for Chesterfield this season, hitting 18 league goals in as many games, and currently comfortably leads the way at the top of the National League's scoring charts.
Despite Salford's more-than-competent defence, it feels a nice bet to back Tshimanga to score at any point in the tie, with the DR Congo-born striker having scored in his last seven consecutive matches.
On the Ammies' side, read Brandon Thomas-Asante as the man in form. He was responsible for that dramatic 95th-minute equaliser that broke Bristol Rovers hearts, and also notched in the win over Oldham.
In addition, Thomas-Asante scored twice in a thrilling 5-3 win over Leeds U21s in the Papa John's Trophy at the beginning of November, and he now has four goals in his last five games.
It feels like this one goes right down to the wire, with Salford having the advantage in terms of league placing, but with Chesterfield looking red-hot right now.
The Ammies have never made it into the FA Cup's third round in their history, and after much consideration, I'm plumping for the option of that run continuing, with non-league Chesterfield winning this one.