The pair are experiencing very different form in League Two, but a Harrogate win would pull them level on points in Group E, with one game in hand.
Match preview
After two contrasting results in their opening EFL Trophy fixtures, Crewe sit second in the group table and can confirm progress by beating League Two rivals this week.
Following a 5-1 thumping of Liverpool Under-21s, the Railwaymen were beaten 4-1 by Blackpool at the start of September, leaving them on three points so far.
Since then, Lee Bell's side have enjoyed a superb run of results, winning five of their last six league matches - including a 3-0 defeat of Harrogate - to move within three points of top spot.
Last time out, they toppled leaders Gillingham, as Shilow Tracey scored his first two goals of the season, striking once in each half to help secure victory for the hosts at Mornflake Stadium.
Having recorded their third straight win - and a fourth consecutive clean sheet on home turf - Crewe will be planning another push for the playoffs this season, and they should be full of confidence when resuming their EFL Trophy campaign.
Harrogate Town have only played once in Group E, beating Liverpool's youngsters on penalties after a 1-1 home draw late last month.
As a result, they have a game in hand on second-placed Crewe and even a draw would keep them in contention until their final fixture, against leaders Blackpool in November.
Simon Weaver's side come into this match searching for form, having followed their midweek mauling by MK Dons with a grim goalless draw against struggling Swindon Town.
Following a 5-1 home defeat and Saturday's 0-0 stalemate in Swindon, the Sulphurites sit 18th in League Two, five points behind Crewe.
Weaver was pleased at his team's response at the weekend, but they have still won just one away game this term, ahead of Tuesday's trip to Cheshire.
Crewe Alexandra EFL Trophy form:
W
L
Crewe Alexandra form (all competitions):
L
W
W
W
L
W
Harrogate Town EFL Trophy form:
D
Harrogate Town form (all competitions):
W
L
D
W
L
D
Team News
Last time out, Lee Bell made only two changes to the Crewe side that lost at Newport County, but he is likely to rotate his squad on Tuesday evening, with one eye on a weekend clash with Doncaster Rovers.
Experienced striker Kane Hemmings is currently sidelined by a foot injury; Omar Bogle and Conor Thomas are also unavailable.
Kian Breckin made his first league start on Saturday and will hope to keep his place in midfield, while Adrien Thibaut and Shilow Tracey - who bagged a brace against Gillingham - could start up front.
Meanwhile, Jack Muldoon and James Daly are set to feature in the final third for Harrogate, while winger Sam Folarin may be brought back into the visitors' starting XI.
Liam Gibson recently suffered a serious hamstring tear that will keep him out of action until 2025, but captain Josh Falkingham has recovered from a knock that saw him benched last time out. The latter can now vie with Matty Foulds for selection at left-back.
Crewe Alexandra possible starting lineup:
Marschall; Knight-Lebel, Demetriou, Williams; Billington, Holicek, Tabiner, Breckin, Conway; Tracey, Thibaut
Harrogate Town possible starting lineup:
Belshaw; Asare, O'Connor, Moon, Gibson; Dooley, Falkingham; Taylor, J. Daly, Folarin; Muldoon
We say: Crewe Alexandra 2-1 Harrogate Town
Crewe are riding the crest of a wave at the moment, so the hosts should take care of business and book their place in the EFL Trophy's knockout phase.