Resuming 11-5 clear, O'Sullivan needed just over 40 minutes to wrap up the win as breaks of 66 in the 17th frame plus a 40 and 65 in the 19th frame - with O'Sullivan conceding 36 points in fouls after nine misses - was good enough to seal his progress.
O'Sullivan has not lost to Williams in a ranking event for the past 10 years, and he was never in danger of subsiding this time against a strangely subdued Welshman, who won the 18th frame to extend the match after O'Sullivan missed a long red late in the frame.
O'Sullivan's reward for victory is a match against 2010 champion Neil Robertson in the last eight. They start their best-of-25 frame match on Tuesday afternoon with O'Sullivan trying to add a fourth world title to his successes in 2001, 2004 and 2008.
"I haven't had an easy draw," said O'Sullivan. "I think whoever wins this tournament will have to beat Neil Robertson and I've got to play him in the quarters so it's definitely not easy. But I'm a competitor, I'll always give it my best and we'll see."
O'Sullivan is the tournament favourite after Judd Trump's surprise loss to Ali Carter earlier in the day.
Williams believes O'Sullivan is a hot favourite to carry off the title. "If Ronnie plays anything like that there's no one left in this competition that can give him any kind of run really. I think Robertson is the only one who could, but he's just so far in front of everyone else it's just frightening.
"You've just got to take your hat off to him and admire what he's doing. It was frightening to watch."
Ronnie O'Sullivan is two frames away from the World Championship quarter-finals after a blistering performance extended his lead over Mark Williams to 11-5 at the Crucible.
O'Sullivan led 5-3 from the opening session on Saturday afternoon between the two former multiple-time Crucible kings, and 'The Rocket' wasted no time doubling his stranglehold from two frames to four with a 107 and a 78.
A break of 51 was enough to take the lead in the 11th frame after Williams had crafted a run of 34, and O'Sullivan was able to hold off the Welshman to claim his third successive frame on the day - his sixth in a row in the match.
The run of six became nine with an almost effortless string of big breaks, following a 68 with a majestic 128 - arguably the second-best break of the tournament thus far, behind Stephen Hendry's maximum - before narrowly missing out on a third century with a 93.
Williams had been far from incompetent during his limited table time, and was finally able to show his worth with a break of 86 to claim the 15th frame and deny O'Sullivan the opportunity to finish the contest with a session to spare.
And just when it seemed that O'Sullivan would end the day just the one frame away from the next round, Williams was able to secure the snooker he needed to snatch the session's closer on the final brown and secure a shred of pride.
O'Sullivan will look for the two frames he needs to complete a resounding victory on Monday evening from 7pm.
Ronnie O'Sullivan leads 5-3 after the opening session of his World Championship second-round match with fellow former world champion Mark Williams at the Crucible.
The three-times champion made five breaks of 50 or more in eight frames, four of which coming within a span of three, but found himself 3-2 down after five.
A pair of 48s and a cracking 86, however, were combined well with some stubborn defensive play to turn the score around and hand the Rocket a two-frame advantage heading into the second session.
Williams, a two-time winner at the Crucible, could only break 50 on the one occasion himself but successfully stifled O'Sullivan with sturdy table control until some crucial errors came back to haunt him.
Many snooker diehards had the second round encounter between O'Sullivan and Williams pegged as a certain classic, guaranteed to entertain. For the first eight frames, it did not disappoint, though the two were not afraid to get stuck into prolonged defensive battles when the time was right.
And in a tough opening frame, O'Sullivan battled for an eternity in search of the snookers that would allow him to snatch the lead, only to eventually succumb to a score of 72-44.
Ronnie would bounce back for 1-1 with two half-centuries in one frame as a 57 was followed by a 52 to level before an unfortunate kiss on the brown denied him a certain century, his eventual 95 more than good enough to lead for the first time.
But although a smooth 56 at the start of the fourth frame made it four big breaks in three, Williams bounced back with his biggest of the session - a 64 - which was enough for 2-2 before a pair of 30+ scores put the Welshman back in control.
O'Sullivan bounced back with a 48 which ended abruptly with a tough middle red refusing to go down, but though Williams came close to mounting a come-back, a missed blue left him requiring a snooker and Ronnie claimed the baulk colours to level once again.
An 86 break at lightning pace put Ronnie ahead once again, and the see-sawing stopped at the culmination of another protracted series of safetys and counter-safetys when O'Sullivan cleared up to the final pink to create a real opening in the balanced contest for the first time.