The holders struggled to break down their stubborn Group D opponents until defender Gerard Pique steered a header beyond goalkeeper Cech in the 86th minute.
Vladimir Darida had a late chance to equalise in Toulouse, only for his well-struck volley to be kept out by David de Gea in stoppage time, but Cech was proud of his side's performance.
"It's always tough with four minutes to go, but I thought we did exceptionally well for 86 minutes. We were constantly under pressure but we managed to block them," Cech told UEFA.com.
"But their talent and quality is huge and they got the goal.
"I made some saves, it's true, I'm pleased with my performance but I thought our defence was exceptional, we made some blocks and filled the spaces.
"But this team is very difficult, they have such quality and invention. You have to defend very well."