Ms Wheeler, a 56-year-old QC and author, married Mr Johnson in 1993 and the pair have four children together.
They separated in 2018 and in February last year reached a financial settlement on their divorce.
Speaking less than a week after Mr Johnson, 56, celebrated his third nuptials with wife Carrie, 33, Ms Wheeler reflected on the end of her marriage and her struggle with cervical cancer, which she was diagnosed with in early 2019.
“The divine plan, it seemed, had gone awry,” Ms Wheeler told the Daily Mail’s Sebastian Shakespeare.
“My four children and I already had tough stuff to handle. My 25-year marriage had become impossible, so I ended it, but the whole business was grinding, so why was I being doled out more?”
Ms Wheeler, who is now cancer-free and last year published her new book, The Lost Homestead, said two years on from her diagnosis she could see she “was lucky”.
She and the prime minister met while attending the European School in Brussels as children, and married after the annulment of Mr Johnson’s marriage to his first wife, Allegra Mostyn-Owen.
Mr Johnson’s personal life has long been under public scrutiny.
The Appeal Court ruled in 2013 that the public had a right to know that he had fathered a daughter during an affair while he was the mayor of London.
Previously, he was sacked as shadow arts minister in 2004 after it was reported he had had an affair with journalist Petronella Wyatt – a year after he married Ms Wheeler.
Mr Johnson currently lives in Downing Street with new wife Carrie Symonds. They have a one-year-old son named Wilfred and got married at a low-key ceremony in Westminster Cathedral at the end of May.
The prime minister has a long-standing policy of refusing to comment on his private life.