George is certainly guilty of premeditated murder and would get a long sentence if the law took the trouble to prosecute him. I think Steinbeck shows that the law enforcement officials would not take much trouble, or go to much expense, to investigate the death of a bindle stiff in those days--especially since Lennie was bound to get killed by somebody. Steinbeck works out the plot so that the murder weapon does not belong to the man who uses it. Carlson owns the Luger, but everybody assumes that Lennie stole it when he fled the ranch. Carlson is in the clear because he is with all the other men when the shot is fired. Carlson hands George the perfect alibi, which is that Lennie had the gun and George took it away from him and shot him in self-defence. The fact that Lennie is such a powerful man would justify George using a weapon against him. It would look a little suspicious that Lennie was shot in the back of the head, but anything could happen if two men are struggling and a gun goes off. It is questionable whether George even thought about making up an alibi when he took Carlson's gun and went to meet his friend. Maybe he didn't care what happened to him. Or maybe he figured that shooting a fugitive who had supposedly murdered a girl would be considered justifiable. Carlson very conveniently provides George with a story, and George just accepts it as the truth which will be related to the police.
"Did he have my gun?"
"Yeah. He had your gun."
"An' you got it away from him and you took it an' you killed him?"
"Yeah. Tha's how."
Morally, I think most readers would agree that George is not guilty. Legally, he is guilty, but the D.A. might have a hard time proving it unless George confessed. Even if the D. A. suspected George of murder, he might decide to ignore the case because of the extenuating circumstances. Lennie had just killed an innocent girl in what appeared to be a rape attempt. Lennie was considered armed and dangerous. Lennie was a psychopath and a menace to society. He was better off dead.
George does kill Lennie, but "guilty" is a loaded word. Legally he is guilty. He shot him. Morally, however, he did not murder him. He killed him because he wanted to make sure that his end was better than if he got caught and tried. He would have been executed either way. George tried to make sure he did not see it coming, to protect him from being scared.
This is a good question and one that we should all ask ourselves upon completing the book.
To look at the idea a little differently, we might ask if George should feel guilty for killing Lennie. The answer to this question, I believe, is no. George did the right thing in shooting Lennie, saving him from a more difficult and confrontational end.
Another question to ask is whether or not George is partially guilty for the death of Curley's wife. George knew what Lennie was capable of and is fully aware fo what happened in Weed. In covering for Lennie, George may be seen as putting others at risk.
Legally, he is definitely guilty. It was clearly premeditated and there's no way it was self-defense. Morally, I do not think he is guilty. I think that he kills Lennie for a good reason. Lennie is probably better off dead at that point. So I don't think we can blame him morally for killing Lennie.
Technically, George is guilty of premeditated murder. However, he killed Lennie because if he did not, Curley and the other men would, and George could not tolerate the idea of Curley torturing Lennie. (Curley planned on just shooting Lennie in the gut just to slow him down.) Even if the men did not kill Lennie, he would have been institutionalized, which would have been a torture as well.