Johnson has four children with Wheeler.
He will say: "So it's ding ding!"
A human rights lawyer Wheeler has exposed Johnson for the door in 2004 and 2010.
Friday's news comes amid predictions that Johnson will soon launch a bid to unseat May as Prime Minister and leader of the Conservative Party.
Despite the impending divorce process, speculation still remains as to whether the former foreign secretary is vying for the top job in Government.
'As friends we will continue to support our four children in the years ahead.
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The former foreign secretary was sacked from the frontbench in 2004, when the mother of an alleged mistress went public with claims of an affair.
Speaking of Johnson's current situation, he said: "He is a husband, a father and I have seen the stuff in today's media about his private life and I think he is entitled to his private life, as indeed is his wife and their children. She will never take him back now", she reportedly told a friend.
'We will not be commenting further'. Johnson was first married to Allegra Mostyn-Owen but the two divorced when he had an affair with Wheeler. The reason was his affair with the journalist Petronella Wyatt and the art expert Helen MacIntyre.
As a Brexit frontrunner within the ruling Tory party, Johnson has credited his wife as a key voice in his decision to support Britain's exit from the European Union (EU) before the June 2016 referendum.
Friends said the pair have been living apart for months and split before Boris resigned as Foreign Secretary in July in protest at Mrs May's Brexit blueprint.