Southerland wound up with 35 points and six rebounds while Brandon Triche and Michael Carter-Williams had 17 each for the Orange.
Syracuse (5-0) was the only one of the 28 unbeaten teams remaining in major college basketball to be in action Thursday.
While Southerland was lighting it up from long range, his teammates went 2-of-13 from beyond the arc.
Arkansas came back from a 14-point deficit in the first half to within two early in the second period before Syracuse began to pull away again.
The Razorbacks (3-3) were led by 25 points from B.J. Young.