Leaving aside moral considerations, which certainly had some influence.
Slavery meant plantation agriculture, and on a national scale, what benefits this tends to work against the interests of developing industry and of free-holding small farmers. A lot of the early sectional friction was over tariffs, which the north wanted high to foster domestic manufacturing, and the south wanted low to hold down expenses in procuring items a plantation economy could not produce locally. Bankers had a mixed view, as most plantations were mortgaged to the hilt, and foreclosure would cost money, but much capital was tied up in such mortgages, which produced less profit than mercantile and industrial investments, or investment in westward expansion of small farming.
The Mississippi River was the great artery for export of Midwestern produce, and products. An independent south controlling this could strangle at will the prosperity of the Midwest. It is worth noting that, while the duel in the narrow space between the capitols at Washington DC and Richmond is the focus of most casual interest and popular history of the Civil War, the main military effort of the Union actually focused on clearing the Mississippi, and it was success it this which sounded the death knell of the secessionists.