The competition's top two leading goalscorers of all-time, considered the best players of the modern era, will continue their long rivalry in a mouthwatering clash.
However, there was confusion when Man United's name was earlier drawn to face Villarreal - a tie which should've been impossible.
And there are suggestions United were not in the pot to face Atletico Madrid.
Elsewhere, Chelsea avoided Bayern Munich, Real Madrid and Ajax by drawing Lille, while Liverpool got RB Salzburg and Man City will face Villarreal in favourable ties.
All four Premier League clubs progressed through to the knockout stages, although Chelsea were the only English side failing to top their group.
The European champions faced a tougher draw when Zenit St Petersburg snatched a last-minute equaliser in a 3-3 draw with the Blues last week.
While Lille won Ligue 1 last season, they were the best-case scenario on current form, while Liverpool and Man City managed to avoid reigning domestic champions such as Atletico Madrid, Inter Milan and PSG.
As Man United discovered, top spot was no guarantee of a favourable route, and they'll now face Messi, Kylian Mbappe, Neymar and co.
Besides being treated to another instalment of Messi vs Ronaldo, the knockout clash could also represent an audition for PSG boss Mauricio Pochettino.
The Argentine is heavily rumoured to be the frontrunner to take charge of the Red Devils when Ralf Rangnick's interim spell ends at the end of the season.
The first legs of the Round of 16 are scheduled for 15/16/22/23 February, with the second legs on 8/9/15/16 March.
Teams who finished as group runners-up will play the first leg at home, although away goals have been scrapped for this season's competition.