Jurgen Klopp's men sailed into the knockout rounds of Europe's secondary competition as Group E winners over Toulouse, LASK Linz and Union SG, bypassing the knockout round playoffs in the process.
In contrast, Sparta Prague were forced to pit their wits against one of the eight teams dropping down from the Champions League on account of finishing second in Group C behind Rangers, which saw the Maroons set up a knockout round playoff tie with Galatasaray.
Sparta suffered a narrow 3-2 defeat in their first leg at Rams Park, but Brian Priske masterminded a phenomenal turnaround in Thursday's second leg, where the reigning Czech champions thumped their Turkish counterparts 4-1 to seal a 6-4 aggregate success.
Three of Sparta's four goals in the second leg arrived in the final 20 minutes, and their reward is a blockbuster fixture with the Reds, whom they met for the first time in the last 32 of the 2010-11 Europa League.
On that occasion, a Sir Kenny Dalglish-led Liverpool were held to a 0-0 draw in Prague before edging a close second leg 1-0 at Anfield, where an 86th-minute Dirk Kuyt header sent the Reds through to the last 16 before their elimination at the hands of Braga.
Liverpool were one of three Premier League teams involved in Friday's Europa League last-16 draw, where Group B winners Brighton & Hove Albion were handed a glamour tie away to last season's runners-up Roma, winners against Feyenoord on penalties in the playoffs.
Meanwhile, reigning Europa Conference League champions West Ham United face an immediate reunion with Freiburg, whom they pipped to first place in Group A with a pair of 2-1 and 2-0 victories earlier in the campaign.
The fourth British team to be seeded for the last-16 draw - Group D winners Rangers - have been paired with former Champions League competitors Benfica, 2-1 aggregate winners against Toulouse in the knockout round playoffs.
The two sides met as recently as the 2020-21 Europa League group phase, where Steven Gerrard's men came away from the Estadio da Luz with a 3-3 draw before letting a two-goal lead slip in a 2-2 stalemate at Ibrox three weeks later.
Elsewhere, Bundesliga leaders Bayer Leverkusen face a taxing journey to Azerbaijani trailblazers Qarabag FK - who saw off Braga 6-5 over an unforgettable two legs in the playoffs - while Marseille will pit their wits against Villarreal.
Having survived a scare against Rennes in midweek, AC Milan will clash with Slavia Prague, and their Serie A foes Atalanta BC are set to take on Sporting Lisbon.
The non-seeded teams will host the first leg of the last-16 ties on March 7, before the return fixtures take place seven days later, but owing to a city clash with Benfica, Sporting and Atalanta's first encounter will be played on Tuesday, March 5.
EUROPA LEAGUE LAST-16 DRAW IN FULL
Sparta Prague vs. Liverpool
Marseille vs. Villarreal
Roma vs. Brighton & Hove Albion
Benfica vs. Rangers
Freiburg vs. West Ham United
Sporting Lisbon vs. Atalanta BC
AC Milan vs. Slavia Prague
Qarabag FK vs. Bayer Leverkusen