The two teams meet in the FA Cup for the first time since the 1957-58 campaign when the Blades secured a 3-0 win over Spurs in the fourth round.
Match preview
After suffering back-to-back defeats to fellow promotion hopefuls Middlesbrough and Millwall, Sheffield United returned to winning way with a hard-fought 1-0 victory at home against Watford on Saturday.
A second-half own goal from Ryan Porteous was enough to separate the two sides in a largely uneventful contest, and the Blades - still sitting second in the Championship table - have now re-established their seven-point cushion over third-placed Middlesbrough, who have played a game more.
Sheffield United are one of seven teams outside of the Premier League who are still competing in this season's FA Cup, and considering their healthy advantage in the race to secure an automatic promotion place in the second tier, Paul Heckingbottom's men can afford to take Wednesday's tie seriously, with a third quarter-final spot in four years up for grabs.
The Blades beat Millwall 2-0 in the third round before battling their way past non-league Wrexham in the fourth round, with an entertaining 3-3 draw in Wales followed by a 3-1 home win in the replay, courtesy of stoppage-time strikes from Billy Sharp and Sander Berge.
Sheffield United have advanced from their last two FA Cup fifth-round ties - beating Reading in 2019-20 and Bristol City in 2020-21 - but coming out on top against Tottenham could prove challenging as they have been eliminated in each of their last five ties at this stage against Premier League opposition.
Following a disappointing 4-1 Premier League loss at Leicester City and a 1-0 defeat to AC Milan in the Champions League, Tottenham Hotspur have responded well with back-to-back 2-0 home victories over London rivals West Ham United and Chelsea.
Emerson Royal and Son Heung-min were both on target against the Hammers, while Oliver Skipp scored his first Spurs goal in the win over Chelsea before all-time record scorer Harry Kane increased his goal tally to 268.
In the absence of head coach Antonio Conte, who continues his recovery from gallbladder surgery, Cristian Stellini has extended his perfect record in charge of the first team to four matches, and the Italian will be hoping for more of the same as they now prepare for three successive away games in three different competitions, starting with Wednesday's trip to South Yorkshire.
Spurs - who sit fourth in the Premier League table - have already beaten lower-league opposition twice in this season's FA Cup, with a slender 1-0 success over Portsmouth in the third round followed by a comfortable 3-0 victory at Preston North End in the fourth round.
However, progressing to the quarter-finals is not a given on Wednesday as they have been eliminated in the fifth round in each of the last three years, including last season's surprise 1-0 defeat after extra time against second-tier side Middlesbrough.
Tottenham have won their last two meetings against Sheffield United, both in the 2020-21 Premier League campaign including a 3-1 victory at Bramall Lane, and another win over the Blades would see them record three in a row for the first time since the mid-1970s.
Sheffield United FA Cup form:
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Sheffield United form (all competitions):
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Tottenham Hotspur FA Cup form:
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Tottenham Hotspur form (all competitions):
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Team News
Sheffield United will be without Billy Sharp (ankle), Rhian Brewster, Rhys Norrington-Davies (both hamstring), Enda Stevens (muscle), Jack O'Connell (knee) due to injury, while George Baldock (hamstring) could be in a position to return to the matchday squad after taking part in training.
Adam Davies has been the Blades' cup goalkeeper this term and he is set to replace Wes Foderingham between the sticks on Wednesday, while Chris Basham will be pushing to start in the back three ahead of either Anel Ahmedhodzic or Jack Robinson.
Manchester City loanees James McAtee and Tommy Doyle will also be hoping to force their way into the first XI, although midfield trio Sander Berge, Oliver Norwood and John Fleck will likely retain their places, with Iliman Ndiaye and Oli McBurnie leading the line in attack.
As for Tottenham, Hugo Lloris (knee), Rodrigo Bentancur (ACL), Ryan Sessegnon (thigh) and Yves Bissouma (ankle) all remain sidelined with long-term injuries.
Rotation is to be expected from the visitors considering their busy fixture schedule, with Pedro Porro, Davinson Sanchez, Japhet Tanganga and Ivan Perisic all pushing to start in defence after watching on from the substitutes' bench against Chelsea.
Pape Matar Sarr could force his way into centre-midfield at the expense of either Skipp or Pierre-Emile Hojbjerg, while Son Heung-min and Arnaut Danjuma are in contention to replace Dejan Kulusevski and Richarlison, with Kane expected to continue as the central striker.
Sheffield United possible starting lineup:
Davies; Basham, Egan, Robinson; Bogle, Berge, Norwood, Fleck, Lowe; Ndiaye, McBurnie
Tottenham Hotspur possible starting lineup:
Forster; Tanganga, Sanchez, Lenglet; Porro, Skipp, Hojbjerg, Perisic; Danjuma, Son; Kane
We say: Sheffield United 1-2 Tottenham Hotspur
Sheffield United have turned Bramall Lane into somewhat of a fortress this season having lost only three of their last 20 home games in all competitions, so their opponents Tottenham - who have lost three of their last five away matches - could be in for an uncomfortable evening on Wednesday.