Manuel will make his first NFL start this Sunday having recovered from minor knee surgery in time for the season opener against the New England Patriots.
The Bills will go into that match as underdogs, but Marrone still has high expectations of his side, especially Manuel.
"I'd be lying if I'm standing here saying that I don't expect him to do great things," ESPN quotes Marrone as saying.
"That's why he's out here. We expect not just EJ, but all of our players that are out there, to perform at a high level. If I lower my expectations of anybody on this team, am I doing my job as a coach?"
The Bills finished last season bottom of the AFC East with a 6-10 record while the Patriots won the division by winning 12 matches and losing just four.