Citizenship and Immigration Minister Charles Sousa and Children and Youth Services Minister Eric Hoskins both quit their posts on Friday.
They join Kathleen Wynne, Sandra Pupatello and Glen Murray as Liberal leadership candidates.
"In the weeks and months ahead, I look forward to the renewal that our party will undergo," Hoskins said in a statement. "I want to be a part of that renewal."
Hoskins will officially launch his campaign at a news conference scheduled for early next week.
Sousa is also expected to officially announce his candidacy when he makes a yet-unspecified announcement in Mississauga on Saturday.
"As we embark in our party's renewal process, I hope to continue to serve Ontarians in the spirit of passion and integrity the premier has exemplified during his time in office," Sousa said in a Friday statement.
Liberal sources tell CBC News that Government Services Minister Harinder Takhar is also planning to enter the leadership race.
McGuinty triggered the competition when he prorogued the legislature and announced his retirement on Oct. 15, saying he'd stay on until a new leader is chosen.
Potential candidates have until Nov. 23 to launch their bids. The party will choose McGuinty's successor the weekend of Jan. 25, in Toronto.