English champions Arsenal have been handed a tough Women's Champions League last 32-clash with Serie A runners-up Fiorentina, while Manchester City will take on Swiss side Lugano.
Scottish champions Glasgow City face a trip to Russia to face Chertanovo, while qualifiers Hibernian will take on Czech side Slavia Prague. It is the first time two Scottish sides have made the knockout stages.
Italian champions Juventus, who have former England striker Eni Aluko, meet Spanish league runners-up Barcelona in the other standout the tie of the round.
City, who finished second in last season's Women's Super League, are seeded and travel to Switzerland first, while unseeded Arsenal are at home first.
Lyon, who have won the last four titles and have England quartet Lucy Bronze, Nikita Parris, Alex Greenwood and Izzy Christiansen in their squad, face Russian side Ryazan-VDV.
Ties will be played over two legs in September, with the first legs on September 11-12 and the second legs on September 25-26.