Prentice says he will run in the constituency of Calgary-Foothills.
The seat opened when Independent Len Webber stepped down this morning to run federally.
"I will work to earn the right to stand up for Calgary-Confederation in Ottawa by running an engaging campaign, and to do this I need to close the chapter on my time as an MLA," Webber, 53, said in a news release.
He left the PC caucus in March to protest what he called the bully tactics and tantrums of then-premier Alison Redford.
Redford resigned soon after as caucus and party discontent mounted over her leadership style and lavish travel and office expenses.
Former energy minister Ken Hughes also resigned today to go back to the private sector.Hughes, a former Conservative MP and rookie PC member of the legislature, said in a news release he is leaving his constituency of Calgary-West to help Prentice pursue his goal of government revitalization.
"Nobody can argue with the analysis that the Progressive Conservative party, the caucus, the cabinet, and the government have needed renewal," Hughes said in a news release.
Hughes said he will return to his former life as a businessman and entrepreneur.
Elected as an MLA in 2012, he served as energy minister and in the municipal affairs portfolio
He ran briefly for the PC party leadership this spring, but withdrew his candidacy soon after to support Prentice.
The Tories won both of the now-vacant ridings by comfortable margins in the 2012 provincial election. Webber collected almost 54 per cent of the vote in Calgary-Foothills. The Wildrose party was second at 33 per cent.
Hughes, with 50 per cent of the vote, beat the Wildrose candidate, who received 37 per cent.
Byelections are also to be held in the constituencies of Calgary-Elbow and Edmonton-Whitemud.
Calgary-Elbow became vacant in August when Redford retired as an MLA ahead of a report from the auditor general on her spending habits as premier.
The Edmonton-Whitemud seated opened up when Dave Hancock, who served as premier after Redford quit the top job, announced earlier this month that he, too, was leaving politics.
A general election is mandated by law to be held in the spring of 2016.
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