Kevin Falcon, Clark's former finance minister and the party's Conservative beacon, announced Wednesday he was leaving his cabinet post and won't be running for re-election in May.
Falcon said he's leaving because his second child is on the way and he couldn't see welcoming a new baby at the same time as ushering in a budget that will form the basis for the next election.
His departure is the first of what could be several high-profile Liberal resignations in the coming days.
Education Minister George Abbott said earlier this week he'd make an announcement on his future shortly.
Energy and Mines Minister Rich Coleman has said he's considering his future and Children's Minister Mary McNeil has said she would like to spend more time with her grandchildren.
Clark said Wednesday people should expect to hear about more resignations.
Liberals who have already announced they won't be running next spring are: Kevin Krueger, Dave Hayer, Harry Bloy, Bill Barisoff, Kash Heed and Murray Coell. Coell is the only cabinet minister among them and Barisoff is Speaker.
Former Liberal cabinet ministers Barry Penner and Iain Black left Clark's government earlier, and their seats were by Opposition New Democrats in byelections last spring.
"This is an opportunity for renewal," Clark said at a Vancouver news conference. "We need to go into the election campaign with a new team."
She said she plans to unveil a team of new candidates that will bring "fresh eyes" to the Liberal party.
"You'll see that over the coming weeks and months, you'll see people that I hope you'll think are really exciting new candidates that are going to bring some of those fresh eyes to the table, because that's what renewal is about," said Clark.
She suggested she is preparing to shuffle her cabinet in the coming days to fill the vacancies she said she expects.
Attorney General and Justice Minister Shirley Bond has been appointed acting finance minister.
Clark discounted speculation that Falcon's resignation leaves a gaping hole in the party's right flank.
Falcon, known for his strong ties to the federal Conservatives and his gung-ho support of the private sector, was deeply committed to ensuring the B.C. Liberals remain a strong free-enterprise coalition that covers and welcomes many political viewpoints, said Clark.
"We are a coalition, we remain a coalition, and I know that Kevin is just as passionately interested in making sure that we get re-elected, as I am, as is anybody who cares about making sure we're creating jobs for people," she said.
Falcon, the runner-up to Clark in the Liberal leadership race in February 2011 and often-touted as the heir-apparent to former premier Gordon Campbell, made a family decision, which is the right decision for him, Clark said.
Clark said the Liberals will regroup as they've done in the past when other party power hitters left government, including former finance ministers Gary Collins and Carole Taylor.
Clark said the Liberals also endured after she left politics to spend more time with her young family.
Falcon bristled at the suggestion he was escaping a sinking ship.
"When people have been in public life for 10, 12, 15, 16 years, you can't say that, because they're leaving, they're jumping ship," he said, while reaffirming his support for the premier.
"I am a strong supporter of the premier and I am a strong supporter of government. One of the things I believe is very important in politics is loyalty. I remain very loyal to our former premier and I remain loyal to this premier."
Falcon also said the B.C. Liberal Party is larger than one person.
"This party has always been a coalition," he said. "We want everyone to feel comfortable under that coalition that is the B.C. Liberals. I will do whatever I can to support my colleagues who are running for re-election."
Falcon did not rule out running for politics at a future date. But for now, he said he's is exploring options in the private sector, though he doesn't yet have another job.
After the leadership vote, Clark appointed Falcon finance minister, giving the Surrey-area politician the daunting task of trying to sell the hated harmonized sales tax to British Columbians.
Voters dumped the tax in a provincewide referendum and Falcon was dutifully overseeing the dismantling of the HST and guiding the return to the previous provincial sales tax, which he often referred to as a "stupid tax."
Falcon represents the riding of Surrey-Cloverdale, where he was first elected in 2001 and then re-elected in 2005 and 2009. He previously served as the minister of health and the minister of transportation.
He excelled as transportation minister, where he managed major projects, including the new William Bennett Bridge across Okanagan Lake in Kelowna.
During the leadership campaign, Falcon courted the business community and often touted tax cuts as the way towards a flourishing B.C. economy.
B.C. Conservative Leader John Cummins, whose upstart party is chipping away at Liberal support in recent public opinion polls, said many conservative-minded B.C. voters may now be looking for somewhere else to vote now that Falcon has left the Liberals.
"He is a federal Conservative and he's seen as the Conservative wing of that so-called coalition and his leave-taking is probably hurtful for the Liberals in the sense that federal Conservatives are going to see one of their stalwarts moving on," Cummins said.
"It could impact on Liberal support."
The Opposition New Democrats were surprisingly cordial in their farewells to Falcon, calling him a solid cabinet minister who knew his portfolios.