In Chapter 1, George tells Lennie that if he were really smart he would leave Lennie and go his own way. He could get a job and keep it while doing whatever he wants to do, even if it means "blowing all his money at the cathouse." This scene between George and Lennie sets up George's love-hate attitude toward Lennie. While he often becomes frustrated with Lennie, George also cares deeply for Lennie. He knows that the companionship that Lennie and he share is worth more than transient jobs. He reminds Lennie of this by telling him that they are different from the other migrant workers because "they have each other."
Moreover, even though George makes the seemingly cruel comment to Lennie, George knows that his dream would be worth nothing with Lennie. In fact, at the end of the book, that is why Candy and he don't go ahead with the dream. It's not truly George's dream.
So, yes, if George were solely logical and wanted only to prosper materialistically in life, he would leave Lennie behind. But doing the "smart" thing often does not satisfy one's human longings.
In Chapter Three, George tells Slim that if he was smart, he would not be working on someone else's land and would instead have a ranch of his own. This would enable him to reap the financial benefits that a ranch hand will never enjoy:
If I was even a little bit smart, I'd have my own little place, an' I'd be bringin' in my own crops, 'stead of doin' all the work and not getting what comes up outa the ground.
To put this comment into context, it comes after Slim calls Lennie a "cuckoo" and remarks that it is strange for George (a man who is "bright") to travel around with him. George's comment, therefore, is a defensive reaction because he feels that Slim has wrongly mocked Lennie's intelligence.
In addition, this comment demonstrates George's deeply-held desire to have his own ranch and to live off the "fatta the lan'." Although this dream seems impossible to achieve in Chapter Three, it does not stop George from believing in it.