Following clashes with Wolverhampton Wanderers and Chelsea, the Foxes will head to South Yorkshire on Saturday (3pm BST kick-off) in search of a 32nd competitive victory over the Blades.
City's most recent league success against Sheffield United came during the 2010/11 Sky Bet Championship campaign, as Andy King's solitary strike sent Sven-Göran Eriksson's men to victory.
As part of a running feature on LCFC.com across the off-season period, we now take a more detailed look at Chris Wilder's men, who sealed the second-tier runners-up spot last season...
The manager
Following a productive playing career which included two spells at Sheffield United, Chris Wilder is one of the most successful managers in recent Football League history.
While the Stocksbridge-born former right-back may only have recently entered the radar of Premier League followers, his record in the lower tiers is incredibly impressive.
Wilder started out at Alfreton Town, where he won the Northern Counties East Football League, League Cup, Presidents Cup and Senior Cup in one season.
Following a six-season stay at Hallifax Town, Wilder moved to Oxford United in 2008, eventually guiding the U's to success in the 2010 Conference Play-Off Final.
Another switch, to Northampton Town, followed in 2014 where, in his second full season, he secured the Sky Bet League 2 title - his first of three Football League promotions.
A move to boyhood club Sheffield United proved too tempting to turn down in 2016 and his maiden season at Bramall Lane ended with them becoming League 1 champions.
After a year of consolidation in the second tier, the Blades launched a magnificent promotion push last season, sealing second place, and ensuring a return to the Premier League.
The squad
With the help of smart loan signings and a talented core of permanent players, the Blades' promotion campaign of 2018/19 should give them confidence in the top-flight.
Top goalscorer Billy Sharp fired 24 goals in all competitions for United, while David McGoldrick's tally of 15 strikes added further firepower to their forward line.
Nine players - Sharp, McGoldrick, Chris Basham, Jack O'Connell, Oliver Norwood, John Egan, John Fleck, Enda Stevens and Dean Henderson - made more than 40 appearances too.
One name in the South Yorkshire side's squad which will be instantly recognisable to Foxes fans is Richard Stearman, a Leicester Academy graduate who has featured 44 times since 2017.
Speaking this summer, Wilder said: "We had a fantastic season and I've thanked the players for their contribution, but attentions have quickly turned to what is set to be another exciting campaign."
The trophy cabinet
Sheffield United's crowning moment came in 1898 as the club lifted the First Division title by a margin of five points over second-placed Sunderland.
However, they have also tasted success in several other competitions in English football, winning the FA Cup four times, in 1899, 1902, 1915 and 1925.
More recent achievements of note include the League 1 title success in 2016/17, and their Championship runners-up berth last season, securing a place in the Premier League.
United have also spent almost half of their 130-year existence in the top division of English football (60 seasons), only dropping into the fourth tier once, in 1982.
Their most recent stint in the Premier League, though, lasted just one season as Neil Warnock's men finished in 18th-place, losing out on goal difference to Wigan Athletic.
The stadium
Sheffield United have played their home games at Bramall Lane - an all-seater ground with a capacity of 32,609 seats - since their formation in 1889.
Remarkably, it is also the oldest major stadium in the world still to be hosting professional association football matches and it also hosted the first floodlit game in the 19th century.
A record crowd of 68,287 crammed into Bramall Lane in 1936, meanwhile, for an FA Cup Fifth Round tie between Sheffield United and Yorkshire rivals Leeds United.
With an average home attendance of 26,177 last season, a visit to the home of the Blades is destined to be a daunting prospect for any Premier League outfit this season.
City's last league victory in South Yorkshire came in 2011 as Andy King found the net in a 1-0 win for the Foxes, who would latter miss out on securing a Play-Off spot in the Championship.