All 16 teams play in the five wealthiest European leagues.
Manchester City's reward for winning its Champions League group was a guaranteed last 16 pairing with a team that only finished runner-up. It got Real Madrid.
The record 13-time champions will host the first leg on Feb. 26 against the ambitious Premier League title holders, who are trying to win the European Cup for the first time.
The match pits Madrid coach Zinedine Zidane against City manager Pep Guardiola. Zidane has won three Champions League titles in three attempts with Madrid, while Guardiola has been seeking his third title for almost a decade after winning twice with Barcelona.
“The only way to be top in Europe is going forward and (playing in) semifinals and finals and winning the Champions League,” City director of football Txiki Begiristain said at UEFA headquarters after Monday's draw.
City's best run in the Champions League was reaching the semifinals in 2016, losing 1-0 over two legs to Madrid. That was soon after Zidane took over in Madrid, and just before Guardiola was hired to replace Manuel Pellegrini in Manchester.
Also, Liverpool was sent back to the Spanish stadium where it won the title last season. The first leg against Atletico Madrid will be at the Metropolitano Stadium on Feb. 18.
“I think that Liverpool know (the stadium) very well,” said Atletico director Clemente Villaverde, describing the unbeaten Premier League leaders as “at this moment the best team we have in Europe.”
Liverpool coach Jürgen Klopp said there were “pretty much four or five potential finals already in the last 16.”
Spanish league leader Barcelona will face Napoli with the first leg in Italy, and Chelsea will face Bayern Munich in a rematch of the 2012 final. Chelsea won that title in Bayern's home stadium, which will host the second leg on March 18.
In other matchups: Paris Saint-Germain coach Thomas Tuchel was paired with his former club, Borussia Dortmund; Lyon will take on Juventus; Tottenham will play Leipzig; and Atalanta will meet Valencia.
Lyon will face Juventus, a team led by Cristiano Ronaldo, without its own star forward. Memphis Depay left Sunday's French league game with a season-ending knee injury.
The Juventus games will be played on the same nights — Feb. 26 and March 17 — as Madrid plays Man City.
“The whole world will be watching, no doubt,” Madrid director Emilio Butragueno said. “We will experience football at its best and then the fans will be lucky to enjoy this kind of game.”
Two pairings feature teams playing in the knockout rounds of the Champions League for the first time. Leipzig will play the first leg at Tottenham and Atalanta will go up against Valencia.
For the first time, all 16 teams left play in the five wealthiest European leagues.
The first legs will be played between Feb. 18 and 26, with the return games from March 10-18.
The final on May 30 will be at the Ataturk Olympic Stadium in Istanbul.
