Vardis Fisher married Leona McMurtrey on September 10, 1917, and their son Grant was born the next year. Their son Wayne was born in 1921. During his studies at the U of U, Fisher did not spend much time in companionship with his new wife. During their separation, Vardis was intensely jealous of any other man who interacted with Leona, often demanding details in letters about people she had spoken with. In September 1924, Fisher told his mother and Leona that he had fallen in love with fellow graduate student Margaret Trusler, and that he wanted to separate from Leona. He explained that if he stayed with Leona, it would cripple his career as a writer to make her happy. On September 8, Leona committed suicide. Fisher blamed himself for her suicide and wrote many poems to her after her death. He later called her suicide the "great crisis" of his life. Their children lived on their grandparents' ranch following Leona's death.