United edged a thrilling playoff with Barcelona 4-3 on aggregate thanks to a 2-1 win at Old Trafford in Thursday's second leg and remain in the hunt for four trophies this season as they continue to improve under coach Erik ten Hag (52).
The English side are looking to secure their first trophy since their 2017 Europa League triumph under Jose Mourinho, with the Portuguese's current side AS Roma pitted against Real Sociedad in this season's last 16.
Arsenal sailed through the Europa League group stages, winning five of their six group matches and take on Sporting next, who overcame Denmark's Midtjylland in their playoff.
Serie A giants Juventus progressed through the playoffs at Nantes' expense thanks to a hat-trick from Argentine forward Angel Di Maria (35) in the second leg in France, and will face Germany's Freiburg next.
Record six-time winners Sevilla are again in the mix, and must negotiate a way past Turkish side Fenerbahce to reach the last eight of this year's competition.
The following is the draw for the Europa League last-16 which was held in Nyon, Switzerland on Friday:
Union Berlin v Union Saint-Gilloise
Bayer Leverkusen v Ferencvaros
Manchester United v Real Betis
The first legs of the last-16 ties will be played on March 9 and the second legs on March 16.
The team mentioned first will host the first leg.
In the third-tier Conference League, English club West Ham United will face AEK Larnaca, Sheriff Tiraspol will play Nice and Basel will take on Slovan Bratislava.
Italian side Lazio will play AZ Alkmaar, Anderlecht will face Villarreal while Gent were drawn against Istanbul Basaksehir.
Turkish side Sivasspor will be up against Italy's Fiorentina and Lech Poznan will face Djurgardens IF.
