Ultimately, Lenny kills Curley's wife. However, to truly understand how this tragedy occurs, it's necessary to look at the events that led up to the woman's untimely demise and how forces shaped both her fate and Lenny's fate as well.
As the novel begins, George and Lennie are walking along a rural California road. They speak of their hope of achieving the American dream: becoming property owners and homeowners. But as the two friends talk, George notices something odd in Lennie's behavior. George demands that Lennie surrender whatever it is that he has in his pocket:
"Come on, give it here." Lennie held his closed hand away from George's direction. "It's on'y a mouse, George." "A mouse? A live mouse?" "Uh-uh. Jus' a dead mouse, George. I didn't kill it. Honest! I found it. I found it dead."
It is the first clue that readers have of Lennie's inability to control his strength. He is attracted to soft and helpless things but he accidentally hurts, and sometimes kills, them.
After the dead mouse is discarded, the reason for George and Lennie's road trip, looking for a new jobs, comes to light. Lennie had become attracted to a woman who apparently had been hanging around their last jobsite. George recalls, at first in a mocking tone:
"Jus' wanted to feel that girl's dress- jus' wanted to pet it like it was a mouse- Well, how the hell did she know you jus' wanted to feel her dress? She jerks back and you hold on like it was...
a mouse. She yells and we got to hide in a irrigation ditch all day with guys lookin' for us, and we got to sneak out in the dark and get outa the country. All the time somethin' like that- all the time. I wisht I could put you in a cage with about a million mice an' let you have fun." His anger left him suddenly. He looked across the fire at Lennie's anguished face, and then he looked ashamedly at the flames.
None of the injuries Lennie inflicts are deliberate but nonetheless, he does cause harm.
George is not blameless in the events that lead up to the death of Curley's wife. When Curley taunts Lennie, and George becomes outraged, even though his rage is justified, what happens is a component of the coming tragedy. When George has had enough of Curley's taunting of his friend, George gives Lennie the go-ahead to defend himself.
George yelled again, "I said get him." Curley's fist was swinging when Lennie reached for it. The next minute Curley was flopping like a fish on a line, and his closed fist was lost in Lennie's big hand.
Grievously injured and nursing hate and revenge, Curley, a man with little empathy in the first place, will feel completely justified when he seeks "justice" for the death of his wife.
Another way in which George contributes to the coming tragedy is when he leaves Lennie at the ranch while he and the other hands go into town to drink and visit prostitutes. Almost everyone on the ranch has gone; seemingly, only Lennie and Curley's wife remain. Both incredibly lonely in their own ways, Curely's wife finds Lennie alone in the barn. Lennie is as attracted to the softness of her hair as he was to the puppy's fur. When he begins to stroke her to vigorously, Curley's wife becomes frightened. She yells and the noise she is making scares Lennie. He doesn't want to get in trouble. He tries to silence the shrieking woman which only make her more frantic. In his panic, Lennie accidentally breaks her neck.
Coming back from their adventures in town, George learns from Candy (who had also stayed behind) of the accidental murder. George sees the scope of events immediately:
"Lennie never done it in meanness," he said. "All the time he done bad things, but he never done one of 'em mean."
George knows that this is the perfect, and justifiable, reason that Curley needs to get his revenge. In a final act of love, George lets his friend know he is not mad, and then he shoots Lennie himself. He will not give Curley and his cronies the satisfaction:
Lennie said, "I thought you was mad at me, George." "No," said George. "No, Lennie. I ain't mad. I never been mad, an' I ain't now. That's a thing I want ya to know." The voices came close now. George raised the gun and listened to the voices. Lennie begged, "Le's do it now. Le's get that place now." "Sure, right now. I gotta. We gotta." And George raised the gun and steadied it, and he brought the muzzle of it close to the back of Lennie's head. The hand shook violently, but his face set and his hand steadied. He pulled the trigger. The crash of the shot rolled up the hills and rolled down again. Lennie jarred, and then settled slowly forward to the sand, and he lay wwithout quivering.