The Grecians have won four and drawn one of their five meetings with Wednesday in the South West, with their last meeting coming in 2012 in League One.
Exeter have a great incentive to progress into the fourth round due to the Owls’ training ground being forced to close due to a coronavirus outbreak, with the Championship side confirming that caretaker manager Neil Thompson and his two assistants are in isolation but would not confirm if any players have tested positive.
Under-18s manager Andy Holdsworth will take charge of the side on Saturday.
Should the Grecians progress, it will be the first time in 40 years that they have progressed into the fourth round of the competition, going onto reach the quarter-finals in that same season which remains their best-ever FA Cup run.
Three-time winners Sheffield Wednesday come into this game unbeaten in four, but this fixture could give several squad players and youngsters some much-needed game time.
Exeter will be without Pierce Sweeney for Saturday’s tie, suffering a hamstring injury on Boxing Day.
Centre-half Rory McArdle looks set to miss out the game against his boyhood club with a knee injury.
However, Josh Key will be in contention for a starting berth after recovering from COVID-19.
Wednesday will be without caretaker manager Thompson and his assistants, who are self-isolating after contracting the virus and will not travel. The club, however, did not confirm if any players also tested positive.
Cameron Dawson, Jack Marriott and Dominic Iorfa all remain out with long-term injuries, whereas Aden Flint was recalled by his parent club, Cardiff City, this week.
Forward Josh Windass is also a doubt after he suffered an injury in the 1-0 victory over Derby County last Friday.
Exeter City (4-4-2):
Maxsted; Caprice, Parkes, Hartridge, Sparkes; Williams, Taylor, Collins, Randall; Jay, Bowman
Sheffield Wednesday (3-5-2):
Wildsmith; Urhoghide, Lees, Brennan; Odubajo, Hunt, Waldock, Dele-Bashiru, Penney; Kachunga, Rhodes
Exeter currently sit 10th in League Two this season after 19 games but are only three points off the playoff positions with a game in hand.
The Grecians are the division's highest scorers, and have netted 24 goals in their last eight games in all competitions.
Last season, the Owls reached the fifth round of the competition, beating Brighton and Hove Albion 1-0 and Queens Park Rangers 2-1 before being eliminated by Manchester City, losing 1-0 at Hillsborough.
Wednesday have won three out of their last four games, however, they were on a 10-game winless streak before their flurry of good results.
Ones to watch
Exeter City – Ryan Bowman
Joint top scorer Ryan Bowman has strung up a superb partnership with Matt Jay, with the pair netting nine goals each so far this season.
The 29-year-old takes on average 2.3 shots per game and produces 0.8 key passes.
Sheffield Wednesday – Fisayo Dele-Bashiru
Saturday’s fixture could be a big game for Fisayo Dele-Bashiru for the midfielder to break back into the first-team picture.
Arriving from Manchester City in the summer, Dele-Bashiru has made eight appearances but hasn’t featured since the end of October.
With the side needing some rotation, the 19-year-old may get his opportunity this weekend in the FA Cup.
Last time they met
Exeter were victorious the last time these two sides met in February 2012.
Jermaine Johnson put the Owls ahead with a magnificent 25-yard drive in the 65th minutes.
However, the Grecians hit back, producing two stunning free-kicks from Billy Jones and David Noble to win the fixture.
In their last seven meetings, Exeter have won five and drawn one against Wednesday, and are also unbeaten against the Owls at home.
What the managers have said
Manager Matt Taylor admits that he doesn’t know what to expect from their opponents, but states that his side must focus on themselves.
"I have no idea what we're going to get from them on Saturday, but I need a clear indication what I expect from my players and that is an aggressive style of play,” said Taylor, speaking to the club’s official website.
"We can only focus on ourselves, and that's what I've said to my players. They'll still be very good players though."
Under-18s manager Holdsworth has expressed his pride ahead of taking charge of the side on Saturday.
He told the Owls’ website: “It all happened really quickly but that’s football and you have to be ready for anything to happen.
“Nothing really changes with how we want to play, the same mantra, same philosophy will apply.
“We won’t be coming in and looking to change the wheel, we’ve had good discussions with Neil and the team, and we want to try and carry on what has been happening. The team are on a very good run and we want that to continue.
“This really is a fantastic club and it’s an exciting opportunity. It has come in a manner that is not ideal but it will be a great experience for us that are involved.
“When you play the game and then go into coaching, you want to be at the highest level you can, of course, you do.
“So it’s an excellent opportunity to understand what it’s all about and learn from it.
“But the be-all-and-end-all is getting in the hat for the next round and for us to have a battle.
“You always should expect a tough game in the FA Cup when you’re away against a side below you in the pyramid.
“This game will be no different, it will be a battle but there is a good confidence here and that comes from winning games.”
Where to watch
The match will be shown live exclusively on BT Sport Extra 5. Commentary only is available on iFollow.