Facing the recently-crowned Premier League champions on their own turf is a daunting enough task in itself, and Villa fans must have been expecting an onslaught from Liverpool as they looked to avenge their 4-0 drubbing to Manchester City only a few days before.
However, Smith's men held out for 71 minutes against the Reds before the quality of Jurgen Klopp's men ultimately shone through, with second-half goals from Sadio Mane and Curtis Jones condemning Villa to yet another defeat in their battle to avoid the drop.
While Villa can certainly take the positives from their game at Anfield, the overall outlook is bleak. Smith's side are now winless in their last 10 in all competitions and have not triumphed in the Premier League since their 2-1 victory over Watford three weeks into the new year.
Villa have no doubt been handed one of the most taxing fixture lists since the restart having faced European-chasing sides in Sheffield United, Chelsea, Wolverhampton Wanderers and Liverpool since the top flight was allowed to resume, and the relegation candidates still have to face Everton and Arsenal after their showdown with Man United.
Five of Villa's seven league wins this season have come on familiar territory, and there should be an extra motivation for Jack Grealish to perform amid persistent speculation linking the Villa captain with a move to Old Trafford.
Meanwhile, United's push for a Champions League berth continues to go from strength to strength as they put five goals past a struggling Bournemouth side on Saturday.
The Red Devils were given an early scare when Junior Stanislas rifled in the opener after just 15 minutes, but the remarkable talent of United's front four soon prevailed as Mason Greenwood, Marcus Rashford, Bruno Fernandes and Anthony Martial put Bournemouth to the sword soon after.
Ole Gunnar Solskjaer's men stretched their unbeaten run across all competitions to 16 games with victory over the Cherries, and United will now endeavour to win their fourth league game in a row when they travel to the West Midlands.
As things stand, the Red Devils currently lie fifth on 55 points - two adrift of fourth-placed Chelsea, who take on Crystal Palace on Tuesday, and the United faithful will certainly be rooting for Palace to take at least take a point off the Blues in the London derby.
A victory for United at Villa Park on Thursday will stretch their unbeaten run on the road to 11 games in all competitions, and the Red Devils have only shipped four goals away from home in that time.
However, Villa managed to salvage a draw in the reverse fixture as the sides played out a 2-2 draw at Old Trafford back in December.
Aston Villa Premier League form: LDLDLL
Manchester United Premier League form: DWDWWW
Manchester United form (all competitions): WDWWWW
Grealish and Tyrone Mings both suffered injury scares last time out but the pair should make the starting lineup for this one, and Smith may opt against making any changes at all to the side that gave Liverpool a good run for their money.
Having had a few days off to recover from their thrashing of Bournemouth, United are expected to announce an unchanged lineup once again.
Victor Lindelof was forced off at half time at the weekend following a back complaint, although the defender's injury is not thought to be serious and he should continue to partner Harry Maguire at centre-back.
Aston Villa possible starting lineup:
Reina; Konsa, Hause, Mings, Taylor; El Ghazi, Luiz, McGinn, Trezeguet; Grealish; Davis
Manchester United possible starting lineup:
De Gea; Wan-Bissaka, Maguire, Lindelof, Shaw; Pogba, Matic; Greenwood, Fernandes, Rashford; Martial
We say: Aston Villa 1-3 Manchester United
United's attacking stars have been in prolific form since the English top flight returned to action, and the Red Devils are now facing a Villa side with the worst defensive record in the league. Smith's side should feel capable of making it a difficult evening for the United backline, but we are expecting Solskjaer's men to continue their excellent run of form with a routine victory at Villa Park.