Lilly served as president of the Chamber from 1996 to 2006.
He left to take a job as Triumph Foods' Chief Administrative Officer.
He said he looks forward to helping local businesses work together.
"The reality is that you compete with a lot of communities here in St. Joseph to represent a unified front," said Lilly. "If you are interested in bringing a business here, we can marshal the resources to make that happen. Making sure we have that foundation of partnership in place will be my first priority."
Lilly takes over for Ted Allison, who announced his sudden exit from the Chamber last year.
The Chamber's Board Chairman, Vern Middleton, said he is thrilled for Lilly's return.
"One of the key things we looked at when we were looking for somebody who could either be already connected with the business community or who could get up to speed quickly," said Middleton. "He is already connected and he is in the business community now, so he brings that credibility that Chamber folks need with the business owners and managers here in St. Joseph."
Lilly is scheduled to take over as the Chamber's leader on March 11.