The minnows are the first non-league club to reach this stage of the competition since 1914.
The sides meet at the Emirates Stadium with under-pressure Wenger knowing an unthinkable defeat against fifth-tier opposition would surely spell the end for him in north London.
Lincoln have already seen off Premier League side Burnley, two clubs from the second-tier Championship and one from the third-tier League One in their remarkable run to the last eight.
They are the first non-league club to reach this stage of the competition since 1914, although they are at the very top of the non-league pyramid, sitting top of the National League and on course to return to the Football League after a six-year absence.
Nevertheless, defeating Arsenal would eclipse all else and go down as the greatest ever FA Cup shock.
And while Danny Cowley's side appreciate the scale of the challenge, they believe they can use the discontent at the Emirates Stadium in their favour.
"The boss said if we can go there and be in the game after 15 or 20 minutes then the crowd might turn on them and we might have 60,000 supporting us instead of 9,000," said skipper Luke Waterfall.
"You never know, it's one of those situations where they want the manager out so there might be a lot of Arsenal fans going to that game wishing we can get something out of that game to see the end of the manager.
"We've got to use it to our advantage.
“The pressure is massively off us this time, all the pressure is on Arsenal.
"They are only fighting on this front now -- the FA Cup is all they've got to play for so they're going to be trying ridiculously hard to beat us and go on and win the FA Cup."
The doubts over Wenger's long reign at Arsenal being extended won't cease if they end Lincoln's run but defeat would pretty much ensure his time was up.
The 67-year-old Frenchman still has the backing of the board despite the humiliation of the 10-2 aggregate score in exiting the Champions League to Bayern Munich in midweek.
The Gunners enter the clash with morale further dented over splits appearing in the squad, Theo Walcott confirming Chilean star Alexis Sanchez had clashed with team-mates prior to the Liverpool defeat last Saturday.
For the Lincoln game, Wenger has continued doubts due to illness over Mesut Ozil, Danny Welbeck and Alex Iwobi.
"I believe that we have two uncertainties: Welbeck, who had to come off after the warm-up against Bayern due to sickness, and Iwobi, who on the day of the game couldn't turn up as well due to the same problem," said Wenger, whose side beat another non-league side in Sutton United in the previous round.
"I haven't decided yet on Mesut, he still felt not too well after the game. I will see in training how he feels and I haven't decided on the team that will start the game on Saturday.
"I don't know if it is a bug or not. I was called on the morning of the Bayern game and told Iwobi cannot play and Welbeck in the afternoon felt sick. We still tried to play him but it could be a bug, I don't know.
"I have always decided to play the team that has a good chance to qualify, and I will continue to do that of course."