Arsenal face seven-time winners AC Milan, while Chelsea take on Napoli who beat Manchester City at the group stage.
It represents possibly the hardest possible draw for the two Premier League sides, who both won their group and were paired with runners-up from the first phase.
Arsene Wenger's side beat Milan at the last 16 stage in 2008 and have advanced on all eight occasions when they have met Italian teams in the knockout rounds, but cannot be happy at drawing the Serie A champions, who finished second in their section behind Barcelona.
Chelsea have not faced Napoli in Europe, but will be wary of a side that knocked out City and boast a potent attacking threat including Edinson Cavani, Ezequiel Lavezzi and Marek Hamsik.
Other highlights include a tie against Bayer Leverkusen for holders Barcelona, while Real Madrid take on CSKA Moscow.
2010 winners Internazionale take on Marseille, while Manchester United's conquerors Basel face Bundesliga outfit Bayern Munich.
"If we remain focused and play with full force then we have a good chance to move into the quarter-finals," said Bayern chief executive Karl-Heinz Rummenigge.
"But please, no underestimating Basel."
This season's final will be played in Munich's Allianz Arena stadium in May.
CHAMPIONS LEAGUE LAST 16 DRAW:
Olympique Lyonnais v APOEL Nicosia
Napoli v Chelsea
AC Milan v Arsenal
Basel v Bayern Munich
Bayer Leverkusen v Barcelona
CSKA Moscow v Real Madrid
Zenit St Petersburg v Benfica
Marseille v Internazionale
*The first legs will be played on Feb. 14/15 and 21/22, with the return legs on March 6/7 and 13/14.
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