Former South Africa all-rounder Klusener had re-joined Zimbabwe's coaching staff in March this year, after previously serving as their batting coach between 2016 and 2018.
Zimbabwe, along with West Indies, Ireland, and Scotland, are part of Group B in the first round at the global event, from which the top two teams will progress to the Super 12 stage.
The African country's first game will be against Ireland in Hobart on 17 October.
"According to his agent, the decision follows Klusener's desire to pursue professional engagements around the globe which will impact his full-time availability for the national team's programmes," Zimbabwe Cricket (ZC) said in a statement.
ZC managing director Givemore Makoni said: "We are grateful to Lance for everything he has contributed during his time with us, including helping us to qualify for the ICC Men's T20 World Cup 2022 which gets underway in Australia in a few days.
"Unfortunately, due to his pressing commitments elsewhere, he could not continue with us on a full-time basis and we agreed it was in the best interests of both parties to terminate his contract. We wish him the best as he pursues new endeavours."
Klusener has already been appointed as head coach of the Durban Super Giants franchise in Cricket South Africa's new SA20 league that is set to start on 10 January 2023.