Williams looked to dominate the baseline exchange from the first point and secured an early break to take charge in the opening set.
Kirilenko kept fighting but a second break of serve secured the first set for Serena inside 30 minutes.
The five-time winner in Melbourne was in complete control early in the second set, breaking at the first time of asking thanks to a series of punishing forehand winners.
Kirilenko tried to to respond but had no answer for a fierce attack from Williams, who raced into a 5-0 lead with her fourth break of the match.
The 31-year-old rounded off a ruthless win in under an hour to set up a quarter-final clash with American teenager Sloane Stephens on Wednesday.