After beginning the game with the advantage, the Orange lost the lead with 10:26 remaining in the first half, with the Cardinals going up 19-18.
Syracuse would fight back to tie the game before the break at 38 apiece.
For the second half, the upperhand stayed with Louisville until the 5:30 mark, when senior guard Brandon Triche fed fellow guard, sophomore Michael Carter-Williams, who connected from deep to take a 64-62 lead.
The lead would switch hands on four separate occasions, while the Orange and Cardinals tied five times.
Triche led four Syracuse players that finished in double-figures in points, with 23.
Junior guard Russ Smith of Lousiville was atop all scorers, ending with 25.
Carter-Williams led the Orange in assists (7), while junior forward C.J. Fair grabbed the most rebounds for Syracuse (8).
With the win, the Orange are now in sole possession of first place in the Big East Conference at 5-0, with the Cardinals moving to 4-1.
Overall, Syracuse improves to 17-1, while Louisville heads to 16-2.
The victory by the Orange will, most likely, oust the Cardinals from the top spot in the country's rankings.
Looking ahead, Syracuse will have little time between this win and their next match, as they return home to host the Cincinnati Bearcats at 3:30pm ET on Martin Luther King Day, Monday, January 21st.