Very possible. Some "close calls"
1) without Lincoln. Like him or not, he kept things wrapped together up north and under a less effective administrator it surely would have unwound.
2) A southern loss at 1st Bull Run. Impact: North thinks the war will be over in 6 weeks and doesn't get the scare in 'em, south resets its agenda and comes on much much stronger in the back half of '61 - with severe consequences
3) AS Johnston lives/wins, and Grant loses an army at Shiloh. Buell was too far away or whatever cause, the net effect is that Grant never holds another command.
4) Hooker stayed in command and totally misses the Confederate advance into Pennsylvania.
5) the Napoleon scenario, where a previously unknown emerges as the Cromwell of the war. This is always a possibility when one calls to Mars in order to solve a problem, and maybe we should all breath a quiet sigh of gratitude this did not happen.
There were a couple other possibilities, but these seem least far fetched.