Barcelona was drawn to face in-form Manchester City, shaped with a strong contingent of Spain internationals by the Catalan club's former director of football. The four-time winner must first travel to Etihad Stadium, where Manchester United and Arsenal have already been routed in the Premier League this season.
"I think Barcelona will be very concerned that they have drawn us," said City coach Manuel Pellegrini, who spent the past nine seasons in the Spanish league. "They are not the team of two years ago."
Chelsea will have an emotional reunion with former striker Didier Drogba when it plays Galatasaray, and defending champion Bayern Munich was paired with Arsenal in the last 16 for the second straight year.
"I'm the luckiest man in this competition in both games I'll be playing home," Drogba, who spent eight seasons at Stamford Bridge, wrote on his Instagram account.
Both City and Arsenal ended up with tough draws after finishing second in their Champions League groups.
"No one of the (seeded teams) wanted to find Man City or Arsenal," said former Barcelona playmaker Luis Figo, who helped conduct the draw. "It's bad luck for Barcelona and Bayern Munich."
Also, nine-time winner Real Madrid will face Schalke, Manchester United got a favourable draw against Olympiakos, Borussia Dortmund will face Zenit St. Petersburg, AC Milan will play Atletico Madrid, and Paris Saint-Germain will meet Bayer Leverkusen.
The first legs will be played Feb. 18-19 and 25-26, with the return matches set for March 11-12 and 18-19.
Man City is the only newcomer to the Champions League knockout rounds, and wasted an opportunity to be seeded when Pelligrini did not realize that one more goal in its 3-2 win in Munich last week would have won the group ahead of Bayern.
Now, it opens the program against Barcelona at home, where the team is averaging more than four goals a game.
"Pelligrini is a very, very good coach," Barcelona director Amador Bernabeu said. "We know from his coaching in Spain that when we play him we have problems all the time."
Manchester City's director of football is Txiki Begiristain, who joined the English club from Barcelona.
"If you want to be champions you need to beat the best ones," Begiristain said. "We have to score in away games in the Champions League."
Chelsea coach Jose Mourinho said last week that Drogba should return to his former club. The Ivory Coast forward's last kick as a Chelsea player was the penalty shootout winner in the 2012 final against Bayern.
The German champions have a re-match with Arsenal, which won 2-0 in Munich last season after Bayern had cruised to a 3-1 win in London.
Bayern coach Pep Guardiola also renews rivalries after his Barcelona team eliminated Arsenal in 2010 and '11.
"I know Arsene Wenger quite well, I know his players quite well," Guardiola said at the Club World Cup in Morocco. "In the draw it was the most difficult team."
Madrid continues its quest for a record 10th European title with a relatively low-key pairing against Schalke.
"On paper, yes, but that is only theory," Real Madrid director Emilio Butragueno said. "Football is unpredictable. It's a German team with a great mentality."
Dortmund, which lost to Bayern in last season's final, got arguably the most unwanted trip — a Feb. 25 visit to Russia to play Zenit in almost certain below-freezing temperatures.
"It won't be easy," Dortmund chief executive Hans-Joachim Watzke said. "But when I look at the teams the other German clubs have to play against, we got through OK."
Leverkusen will be at home first against big-spending PSG and its feared forward line of Zlatan Ibrahimovic and Edinson Cavani.
"You don't have to be an expert to say we are the outsiders," said Leverkusen sporting director Rudi Voeller, whose team lost 5-0 at home to United last month.
PSG coach Laurent Blanc said it "could have been worse," but then added: "If they are second to Bayern it means they are a talented team."
AP Sports Writer Paul Logothetis in Agadir, Morocco, contributed to this report