The governing Liberals are seen to be vulnerable in the north and eager to hold on to seats in the Greater Toronto Area, but Wynne said that wasn't a factor in her decision.
She said all 107 ridings in the province are key ridings.
"Again, I made these decisions based on people's experience and their capacity to do the job. That really was the calculation that I made."
Bill Mauro from Thunder Bay-Atikokan became the new municipal affairs and housing minister, taking over from Linda Jeffrey who resigned earlier in the day to run for mayor of Brampton.
Oakville's Kevin Flynn got the labour portfolio from Yasir Naqvi, who became minister of community safety and correctional services.
Madeleine Meilleur, who held that portfolio, was named Ontario's first francophone attorney general and retains her responsibility for francophone affairs.
Her predecessor John Gerretsen, who has said he won't run for re-election, is minister without portfolio and chairman of cabinet — taking over from Jeffrey.
Wynne has enlarged her cabinet to 26 ministers at a time when her government is trying to cut costs to battle a $12-billion deficit. There's also one less woman at the table.
The premier, who has spoken out about the importance of women in politics and noted that Jeffrey was the first elected woman to represent Brampton provincially, said gender wasn't a factor when she drew up her cabinet list.
Choosing a cabinet is a difficult process, said Wynne, adding that she based her decisions on the capacity of the candidates to do the job.
"I'm proud of the work that the women in our cabinet do and I'm proud of the work that the men in our cabinet do," she added.
"I'm very confident that these are the people who can carry these portfolios forward in the best way."
But it's a strange coming from a premier who said she wouldn't be surprised if the recent ouster of Alberta Premier Alison Redford was partly driven by sexism, said Progressive Conservative Lisa MacLeod.
"For somebody who talks a lot about gender and politics, she absolutely scored an 'F' in terms of losing a female cabinet minister and then picking up two men," MacLeod said.
The shuffle is a desperate attempt to save seats in regions where the Liberals are vulnerable, she said. It's also a missed opportunity for Wynne to turf ministers who should have been fired for scandals under their watch.
MacLeod said Tourism, Culture and Sport Minister Michael Chan has allowed runaway spending for the 2015 Pan Am Games and Health Minister Deb Matthews has hung on to her job despite a criminal investigation into shady dealings at Ornge, the province's publicly funded air ambulance service.
Flynn was the lucky beneficiary of an expensive seat-saver program when the Liberals cancelled an unpopular gas plant in his riding ahead of the 2011 election, sticking taxpayers with an enormous bill, she said.
"And now we see he's getting a cabinet post as well," MacLeod added.
Jeffrey said she left her job over spending scandals — just not Liberal ones.
She was troubled by the controversies surrounding current Brampton Mayor Susan Fennell, Jeffrey said, which include a sky-high salary and the approval of hundreds of millions of dollars for projects that weren't completed or started.
But Jeffrey said she stands by the Liberals' decision to cancel the gas plants — one in Oakville and another in Mississauga — despite the estimated $1.1-billion price tag that will likely become political cannon fodder in the mayoral race.
"It was a difficult decision, but I'm focused on what's happening in Brampton," she said.
"Right now, I see some very troubling things that are being discovered on a daily, weekly basis. I think respect for taxpayers is an extraordinarily important quality and I plan to bring that to the job."
Wynne has six months to call a byelection in Jeffrey's riding of Brampton-Springdale, unless there's a general election. If the Liberals can't pass their spring budget, the government will fall and voters will be sent to the polls.
Jeffrey said she's been lobbied to run for mayor of Brampton over the past year, with former Progressive Conservative premier Bill Davis — who represented his hometown in the legislature — being one of the most vocal proponents.
But she said she's only been considering it seriously since January.
Jeffrey is the latest Liberal to announce that she's calling it quits since Wynne took the top job just over a year ago.
Laurel Broten quit last July, following her cabinet colleagues Margarett Best, Dwight Duncan, Greg Sorbara, Chris Bentley and former premier Dalton McGuinty. Backbencher Kim Craitor also stepped down.
Joining the exodus are Gerretsen, Government Services Minister John Milloy, former cabinet ministers Rick Bartolucci, Harinder Takhar and Donna Cansfield, as well as MPP Phil McNeely, who have all said they don't plan to run again.