While City have previously competed in the UEFA Champions League and the UEFA Cup, the current campaign is the Club's maiden appearance in the Europa League.
However, Brendan Rodgers' men have acclimatised well to their new surroundings, securing victories over Zorya Luhansk, AEK Athens and SC Braga in Group G.
Ahead of Thursday's first leg in Prague, LCFC.com looks back as City's European exploits so far...
Leicester City's Europa League debut pitted the Foxes up against Ukrainian outfit Zorya Luhansk on Filbert Way on 22 October - the first act of a six-game winning run in all competitions.
City took the lead after just 29 minutes after Harvey Barnes' effort came back off the post into the path of James Maddison to open his account in Europe.
A neat flick from Kelechi Iheanacho, meanwhile, set Barnes through to write his own name on the scoresheet, before Iheanacho followed suit with a neat turn and finish with 23 minutes remaining.
“We want to do well,” Brendan Rodgers told LCFC TV at full-time. “There's no doubt. We worked so hard to get in it and to arrive in Europe, so I don't see the point then of changing it.
“We don't really have the depth to do that, to be honest, with so many players out injured. We want to be strong. The players want to improve and challenge both in the league and in Europe.”
The Foxes made it two from two in Europe with a hard-fought 2-1 success over AEK Athens at the Olympic Stadium in the Greek capital on 29 October.
Jamie Vardy's 18th-minute spot-kick sent Leicester on their way before a Hamza Choudhury half-volley doubled the visitors advantage before the half-time break
There was cause for alarm, though, as Muamer Tanković got a goal back for AEK, before also firing over from close range as the home side looked for a leveller which ultimately didn't come.
"We're really, really pleased," Choudhury said afterwards. "In Europe, especially, it's important to do well in your away games. It can be really tricky coming to clubs like this away from home.
"It's a new experience for a lot of us, but like the manager said in there, he's really proud and I think we all should be, coming here and getting a result like we have so it's a really big three points."
City's biggest-ever victory in European competition enabled Brendan Rodgers' men to open up a three-point lead at the top of Group G as they saw out a 4-0 home success over SC Braga on 5 November.
Following an impressive 4-1 triumph at Leeds United in the Premier League, Kelechi Iheanacho bagged a brace for the Foxes at Leicester City Stadium against Portuguese opposition.
The Nigeria international also laid it up for Dennis Praet to score his maiden European goal for the Club, before James Maddison skipped into the penalty area to wrap up a memorable evening.
"Yes, we are strong in the Europa League now, so three wins," Iheanacho said. "We'll keep going. Keep our focus and hopefully, in the next games, we keep winning.
"It's enjoyable, we love it. So, we'll keep working really hard to get to the highest level, so hopefully we'll get to the top in Europe."
A helter-skelter encounter with Braga in the return fixture at Estádio Municipal de Braga, on 26 November, was next up for the Foxes, who knew qualification was within their sights.
Leicester, though, came across a far sterner opponent in their second clash with Carlos Carvalhal's men and the home side took the lead through Al Musrati, drilling a low effort into Kasper Schmeichel's bottom corner.
City hit back almost immediately, as Harvey Barnes riffled into the top corner, but Braga hit back and took the lead again with Paulinho on the scoresheet.
It would remain 2-1 to Braga for much of the second period, too, until James Maddison threaded a smart pass into Academy graduate Luke Thomas to bundle in his first goal for the Club.
Fransérgio thought he'd won it for the home side with seconds to spare, but up popped James Vardy with a close-range finish - after excellent work from Marc Albrighton - to rescue a point which sealed qualification.
With their place in the Round of 32 already secured, Leicester were able to welcome Wilfred Ndidi, Ricardo Pereira and Çağlar Söyüncü back into the starting line-up for a tricky away test at Zorya Luhansk.
Although Söyüncü was forced to withdraw in the first half, Ricardo and Ndidi enjoyed run-outs lasting 45 and 55 minutes respectively, but the Foxes couldn't find a way through Zorya's stubborn defence.
Cengiz Ünder, Wesley Fofana and James Maddison all had chances to take the lead for City, but ultimately it fell for Allahyar Sayyadmanesh, six minutes from time, to seal an admirable win for Luhansk on 3 December.
"It was just unfortunate, I feel, for the players because they put so much into the game," Brendan Rodgers said. "They showed a great desire to want to win the game, even though we had a couple of injuries to deal with."
Leicester headed into matchday six, the final round of group stage fixtures, knowing they needed to match Braga's result to secure top spot in Group G, ahead of the Round of 32 draw.
And they did just that, racing into a two-goal lead over AEK Athens within the opening 14 minutes. Cengiz Ünder and Harvey Barnes were both on target for the Foxes at Leicester City Stadium, rounding off a memorable start to their first European campaign since 2016/17.
Brendan Rodgers commented after the match, which finished 2-0: "We mentioned about making a quick start. We wanted to finish in first place and cap off a good competition so far. The players responded to that really, really well.
"We’ve been very strong in that opening sector of the game, and in the first 25 minutes, we played with a really good intensity and speed, and scored two quality goals with opportunities to score more."