The Foxes will make the trip south to the newly-opened Brentford Community Stadium this weekend, following a meeting at Griffin Park at the same stage of the 2019/20 competition.
City, unbeaten in seven games in all competitions, tackle the Bees, who currently sit in the Sky Bet Championship play-off places, after both sides progressed from the third round.
Ahead of a first competitive encounter between the two sides at Brentford's new home, LCFC.com continues to give the lowdown on each of Leicester's 2020/21 opponents...
The team
Summer signing Ivan Toney is the only player to have started every Championship fixture so far this term, while Bryan Mbeumo has also featured in all 23 games. Mbeumo, a France Under-21 international, is currently leading Brentford's assist charts with six, just ahead of Mathias Jensen (5).
Toney, recruited from Peterborough United for a reported £5M, is also the Bees' top scorer by some distance, with 16 goals to his name in 2020/21. The forward's first came from the penalty spot against Millwall in September.
Two significant summer departures came in the form of attacking talents Ollie Watkins and Saïd Benrahma who, after helping Brentford reach the Championship play-off final last term, both left to join Premier League clubs Aston Villa and West Ham United respectively.
The manager
Danish manager Thomas Frank has been in post since October 2018 after serving as Dean Smith's assistant before the 49-year-old's departure to Aston Villa, who he later guided to promotion.
After 18 years in youth coaching, working with Frederiksværk, Hvidovre IF, B93, Lyngby and various levels of the Denmark youth set-up, he managed Brøndby IF between 2013 and 2016.
Despite finishing fourth and third successively in the Danish Superliga, Frank's Brøndby side failed to reach the UEFA Europa League group stages, and he resigned from the role in March 2016.
Following a two-year stint within the Brentford coaching team, he was promoted to the manager's position in the days following Smith's exit to Villa Park, finishing 11th in the Championship in 2018/19.
Last term, Frank's Bees reached the play-offs, finishing third at the end of the regular Championship season and narrowly missing out on automatic promotion, before beating Swansea City over two legs in the semi-final.
The final, however, went Fulham's way, with Brentford's west London rivals winning in extra-time at Wembley to gain promotion to the top flight.
Form guide
Thomas Frank's side defeated Championship rivals Middlesbrough to reach the fourth round stage. Goals from Halil Dervişoğlu and Saman Ghoddos were enough to see the Bees through at Brentford Community Stadium.
Brentford's cup run in the Carabao Cup, meanwhile, took them all the way to the semi-final, where they met Tottenham Hotspur. Played four days before their FA Cup success, the Londoners were defeated 2-0 by José Mourinho's side.
In the league, Brentford are aiming to go one better than last season and gain promotion to the Premier League. The Bees ended 2020 with three consecutive wins over promotion hopefuls, beating Reading, Cardiff City and AFC Bournemouth, scoring eight goals in the process.
In fact, they have not lost in the league since 24 October, an unbeaten run currently standing at 15 games. Their league record of three defeats is the lowest number of any Championship team so far this season.
Previous encounters
Last season's fourth round draw pitted the two sides together at Griffin Park for the first time since 1993 with Leicester coming out on top 1-0 thanks to Kelechi Iheanacho's early strike.
The Foxes are unbeaten in the last seven meetings, winning six of those, in a run stretching back to 1953. This is the fifth time that the pair have been drawn together in the FA Cup, with Leicester progressing on each previous occasion.
In 1947, it took two replays to finally decide the winner, with City eventually triumphing 4-1 after two goalless draws.
The trophy cabinet
Brentford lifted the old Second Division title in 1935 before going on to secure their all-time best league finish in the top tier - fifth place - the following season.
They have also won the third division on two occasions, most recently in 1992, while finishing runners up on four occasions, lastly in 2014.
Three fourth division titles are included on Brentford's honours list, too. In cup competitions, the Bees have reached the quarter-finals five times and been beaten EFL Trophy finalists on three occasions.
The stadium
Brentford's 116-year stay at the 12,300-capacity venue, Griffin Park, came to a close in the summer when the club moved to the Brentford Community Stadium.
Their new home, a state-of-the-art venue in west London, is a 17,800-seater stadium which they share with fellow tenants, London Irish.
The first match at the stadium took place on 1 September 2020 as Brentford drew 2–2 with Oxford United in a pre-season friendly, ahead of the first competitive fixture against Wycombe Wanderers in the first round of the Carabao Cup, which the hosts won on penalties.
The fixtures
Following Saturday's Emirates FA Cup clash with City, Brentford travel to meet Swansea City at Liberty Stadium on Wednesday 27 January (7pm kick-off) before hosting Wycombe Wanderers on Saturday 30 January (3pm kick-off).
Thomas Frank's side are at home again on Tuesday 2 February, taking on Bristol City (7pm kick-off), before consecutive away games against Middlesbrough and Reading.
All times GMT.