The Lions edged out Wycombe Wanderers to make it this far in the tournament, while Oliver Glasner's men have already eliminated Norwich City and Queens Park Rangers from this year's edition.
Match preview
A master of the knockout arts, Aston Villa boss Unai Emery has proved as such throughout the early stages of the 2024-25 season - just one look at the 36-team Champions League table that the Lions sit at the summit of is evidence of that.
A trip to Wycombe was never expected to pose any serious threat to Villa's hopes of EFL Cup glory, although they made harder work of booking their spot in the fourth round than they needed to, as Emi Buendia and Jhon Duran struck before a late Chairboys consolation from Richard Kone.
While that injury-time goal had no bearing on the overall result, a dejected Villa were left to rue an injury-time intervention in Saturday's Premier League visit of Bournemouth, as Evanilson dramatically stole a point for the Cherries with 96 minutes gone on the board after Ross Barkley's opener.
As gut-wrenching as that 1-1 stalemate was, Villa could at least take the small victory of extending their unbeaten run in all tournaments to 11 matches, but not since losing in the final of the 2019-20 edition have they gone further than the fourth round of the EFL Cup.
Furthermore, the Lions have to go back to pre-lockdown times for their last home victory in the competition, losing each of their last two EFL Cup games at Villa Park to Stoke City and Everton since besting Leicester City 2-1 in January 2020.
As Villa continue to compete in the upper echelons of the Premier League table, Palace find themselves scrapping with the basement boys after a severe fall from grace under 2022 Europa League winner Glasner.
However, the ninth time proved to be the charm for the Eagles on Sunday afternoon, as after failing to win any of their first eight top-flight games of the season, Palace deservedly triumphed 1-0 over a timid Tottenham Hotspur side thanks to Jean-Philippe Mateta's first-half finish, aided by an outrageous Eberechi Eze assist.
Before belatedly getting off the mark in the top flight - and clambering out of the relegation zone in the process - the EFL Cup provided Palace with a safe haven, as Glasner's team battered Norwich City 4-0 in the second round before eking out a 2-1 triumph over QPR in their last knockout affair.
A first last-16 appearance since the 2018-19 campaign now awaits a Palace side still searching for their maiden major trophy, but not since the 2011-12 season - when they lost to Cardiff City in the semi-finals - have they been past this point of the EFL Cup.
The Eagles have also gone winless in their last seven trips to Villa Park in the Premier League - losing four of their last five - but more recent memories of facing Emery's team are much fonder; Glasner's men memorably embarrassed the Champions League leaders 5-0 at Selhurst Park the end of the 2023-24 season.
Aston Villa EFL Cup form:
W
Aston Villa form (all competitions):
D
W
D
W
W
D
Crystal Palace EFL Cup form:
W
W
Crystal Palace form (all competitions):
W
D
L
L
L
W
Team News
Villa were only missing one player for the weekend's draw with Bournemouth - Jaden Philogene was suspended on account of his red card against Fulham - but the winger's return means that the hosts have a clean bill of health for the last-16 tie.
Philogene is among the second-string players in line for starting roles on Wednesday, a list that also includes Saturday's goalscorer Barkley, who should replace Amadou Onana given that the Belgian has been taken off at half time in each of the hosts' last two matches.
Wednesday's game should also be a brilliant opportunity for Tyrone Mings and Boubacar Kamara to build their minutes back up after serious knee injuries; both were on the bench against Bournemouth and the latter came on as a late substitute.
Regarding Palace's availability, Glasner is still without the injured quartet of Chadi Riad (knee), Chris Richards (thigh), Matheus Franca (adductor) and Cheick Doucoure (toe), while Rob Holding remains out of the first-team picture due to his falling-out with the head coach.
The Eagles doctors also welcomed two new faces into the treatment room at the weekend, as Jefferson Lerma had to be withdrawn in the first half of the win over Spurs due to apparent muscle discomfort, before Ismaila Sarr was also unable to complete the full 90.
The latter's issue does not appear too severe, but Daichi Kamada should be brought in to freshen the team up, while Will Hughes is set to step in for the stricken Lerma in a deeper midfield position.
Aston Villa possible starting lineup:
Olsen; Nedeljkovic, Mings, Carlos, Maatsen; Kamara, Barkley; Bailey, Buendia, Philogene; Duran
Crystal Palace possible starting lineup:
Henderson; Guehi, Chalobah, Lacroix; Munoz, Wharton, Hughes, Mitchell; Kamada, Eze; Nketiah
We say: Aston Villa 1-1 Crystal Palace (Villa win on penalties)
Palace boss Glasner went incredibly strong for the third-round win over QPR and can afford to do so again with no European football to take into account, which is more than can be said for the Villans.