The 2014 champion has done it tough in the opening week, but despite the tight scoreline, he was rarely threatened by 89th-ranked Seppi on a sunny afternoon at Margaret Court Arena.
With top seed Andy Murray crashing out only minutes before the win, Wawrinka's chances of grabbing a fourth grand slam title have been given a huge boost and he is now the highest seed in the top half of the draw.
Wawrinka next faces Dan Evans or Jo-Wilfried Tsonga for a place in the semi-finals.