Hancock was emotional as he spoke at Government House in Edmonton.
With his wife Janet at his side, Hancock choked back tears as he spoke about how families are affected by life in the public eye.
"Very few people understand the toll that politics takes — on families," he said as she placed her hand on his shoulder. "It's a consuming job. And finding that balance between family and province is probably the most challenging task."
The Progressive Conservative caucus named Hancock interim premier and party leader after Alison Redford resigned in March.
Hancock's time in the province’s top political job will end when new PC leader Jim Prentice is sworn-in on Monday.
He told reporters that he hasn't yet submitted his resignation letter but expects the seat will be vacated in time for the byelections expected to take place this fall.
A lawyer and long-time PC party member, Hancock was first elected in 1997. He served in cabinet in eight different portfolios under premiers Ralph Klein, Ed Stelmach and Alison Redford.
Hancock also served as House Leader during most of his time in the legislature. He paid tribute to PC caucus members as well as MLAs from opposition parties.
"I've worked with some really great people from all parties and from all caucuses who want to do the best thing for Alberta," he said. "And I would hope that as we go forward we can continue to honour and respect service and the people who provide service because it's not an easy job."
In a statement, Wildrose leader Danielle Smith wished Hancock and his family well.
“While we have shared no shortage of disagreements in our day-to-day battles in the legislature, there is no question that Premier Hancock has shown a strong dedication to our province with his passion towards public service," she said.
"Mr. Hancock leaves office with a well-deserved reputation as a top-notch parliamentarian, hard-working local representative, and dedicated family man."
Hancock's resignation from Edmonton-Whitemud leaves a seat open for former Edmonton mayor Stephen Mandel.
There is much speculation that Mandel, a member of Jim Prentice's transition team, will be one of the people named to cabinet on Monday.