The French side, under Leonardo Jardim, sprung a surprise 3-1 victory over Arsene Wenger's Gunners at the Emirates Stadium to confidently set up a return bout at home on March 17.
Goals from Geoffrey Kondogbia and Dimitar Berbatov preceded Alex Oxlade-Chamberlain's injury-time response before Yannick Ferreira-Carrasco heaped a little more misery on the north Londoners with a third goal at the death.
Turkey international Hakan Calhanoglu produced a stunning angled finish in the 57th minute before Atletico's Tiago was sent off for a second yellow card in the 76th minute giving the German side a slight advantage going into the return leg at the Vicente Calderon.
Tuesday night saw Barcelona edge Manchester City 2-1 at the Etihad Stadium courtesy of a first-half brace from Luis Suarez but the deficit was reduced when Sergio Aguero struck with just over 20 minutes remaining prior to Gael Clichy's 74th-minute sending off.
Italian champions Juventus gave themselves a slender lead by getting the better of Borussia Dortmund 2-1 in Turin with Carlos Tevez and Alvaro Morata netting either side of Marco Reus' 18th-minute leveler.
Chelsea produced a satisfying 1-1 draw with Paris Saint-Germain at Parc des Princes which saw Edinson Cavani cancel out Branislav Ivanovic's opener while Real Madrid took another step towards defending their European title by beating Schalke 2-0 in Gelsenkirchen thanks to goals from Cristiano Ronaldo and Marcelo.
The return legs will take place on March 10-11 and 17-18 to determined which eight clubs move through to the quarter-finals of Europe's premier club competition.
2014/15 UEFA Champions League - Round of 16 first leg scores
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