Both sides are in excellent form and are among the heavy favourites to win promotion in their respective divisions this season.
Match preview
Chesterfield are no strangers to being handed devilishly difficult FA Cup ties, and they have gotten another one here, facing the highest-ranked side in the competition.
The Spireites did not even qualify for the competition proper in both 2019-20 and 2020-21 as they were drawn against Wrexham and Stockport County respectively, arguably the two strongest non-league sides at the time.
Since then, Chesterfield have made notable progress, mixing it with the big boys by reaching round three in both of the previous two seasons.
After going down to at-the-time European Champions Chelsea in 2021-22, Chesterfield then forced Championship West Bromwich Albion to a replay last season.
Having faced two of the strongest National League sides in recent memory in qualifying though, Chesterfield are now the team to beat in non-league.
Paul Cook's side thrashed Kettering 5-0 to reach this stage, and they are current National League leaders, with only Barnet in pursuit.
Chesterfield are still two points ahead though, and have a game in hand over their only real challenger for top spot, having taken 44 points from a possible 51 so far.
While now on a run of five straight wins, Cook's men also went almost seven-and-a-half hours without conceding until Zak Brown's equaliser for Kidderminster Harriers last weekend, before eventually winning 3-1.
Having retained almost the entirety of the squad which pushed Notts County so close in the playoffs last season, Chesterfield are highly-fancied to go up, and Saturday's 3-1 win was the 10th time they have scored three or more goals already this season, after just 18 games.
Chesterfield will relish the challenge of facing the side currently dominating League One, as Portsmouth look set for a long-awaited return to the Championship after 12 years away.
John Mousinho's side are still unbeaten in the league and have taken a superb 35 points from their opening 15 matches.
Pompey are yet to lose in 90 minutes in any competition, as their only defeat so far came on penalties to Peterborough United in the EFL Cup.
The League One leaders kept up their fine start with a remarkable comeback away at struggling Reading last weekend.
Despite being stunned early on, going 2-0 down inside the opening half hour, Pompey rallied and came back to win 3-2 thanks to goals from Tino Anjorin, Colby Bishop and Terry Devlin.
The Portsmouth faithful will be hopeful that their current form can also lead to better fortunes in this competition, one they have struggled in since being winners in 2008 and finalists in 2010.
After slipping out of the Championship and entering at the first round, Pompey struggled to navigate the early stages, suffering exits at the first hurdle in five of the first six seasons after.
Some success has since followed, as they reached the last 16 in 2020 and got to the third round last season, before going out to North London's finest Arsenal and Tottenham Hotspur, respectively.
Chesterfield FA Cup form:
Chesterfield form (all competitions):
Portsmouth form (all competitions):
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Team News
Everton loanee Harry Tyrer has missed the last two games for Chesterfield with a back problem, so Ryan Boot is expected to keep his place between the sticks.
Will Grigg is in excellent form for the hosts, netting three in his last two to take his tally to nine for the season, more than he managed in 48 appearances for MK Dons last season.
Albanian youth international Armando Dobra will likely be the main creative threat for Chesterfield, starting on the left flank.
Mousinho may rest a few players with their promotion push in League One likely to take priority.
The young manager will be without a fair few first-team players though, including Conor Ogilvie, who went off injured inside the opening 10 minutes against Cambridge United recently.
Anthony Scully, Tom Lowery and Marlon Pack are all also absent for the visitors, so last week's match winner Devlin may get another start after coming into the side at Reading.
Chesterfield possible starting lineup:
Boot; Mandeville, Williams, Grimes, Freckleton; Naylor, Jones, Banks; Colclough, Grigg, Dobra
Portsmouth possible starting lineup:
Schofield; Swanson, Raggett, Towler, Sparkes; Stevenson, Devlin, Robertson; Lane, Saydee, Anjorin
We say: Chesterfield 2-4 Portsmouth
In what could be a thriller between two of the most in-form teams in English football, Portsmouth's class and higher-level experience may just get them over the line.