The North had two major weaknesses in the Civil War.
The first had to do with its military abilities. The North did not have much of a warrior culture. Many more Northerners than Southerners lived in cities. Southerners were much more likely to know how to ride horses (an important military skill in those days) and shoot guns. The South also had much more of a tradition of soldiering. Because of this, many of the best officers in the US Army left the army when the South seceded. Robert E. Lee is the most notable example of this.
The second weakness has to do with strategy and war aims. In order to win, the North had to completely defeat the South. It had to invade the South and conquer it. The South, by contrast, could potentially win the war simply by going on defense and preventing the North from defeating it. The North would get tired of the war and would give up just as the British had in the Revolutionary War.
These were the two main weaknesses faced by the North.