The table-toppers turned in a stellar performance as they fully stretched bottom-of-the-league County, who spluttered against the high tempo of the home side.
Lisbie started the goal rush in the 28th minute when he ran on to a superbly delivered Lloyd James free-kick and headed the ball down and past Bartosz Bialkowski.
His second on the stroke of half time owed much to good refereeing by Rob Lewis, who played the advantage allowing David Mooney to race down the left before threading the ball through to Cox.
The diminutive midfielder's shot was blocked, but the ball rebounded to Lisbie who drilled the home from 15 yards to give the O's a comfortable lead at the break.
Cox himself added to the party atmosphere 11 minutes into the second period when he curled his low shot into the net off the far post.
In a rare Magpies raid, unmarked substitute Danny Haynes pulled a goal back with a header, before Shaun Batt restored the three-goal advantage - squeezing a shot past Bialkowski after scampering away from two defenders.
County's miserable night continued when Jayden Stockley netted in the 84th minute to record his first goal since joining Orient on loan from Bournemouth.
Butler made no mistake with a neat close-range finish in the 69th minute as Wolves' record of five successive league victories came to a shuddering halt.
Dean Smith's Walsall side had lost on penalties to Wolves at Molineux in the Johnstone's Paint Trophy two weeks ago to make their league success all the sweeter.
Having ended a run of five league and cup games without a win by beating Crewe 3-0 last weekend, Butler earned Walsall their second successive league success when he converted a knock down from James Baxendale following Andy Taylor's left-wing free kick.
The margin of their success could have been greater as Milan Lalkovic hit the post in stoppage time.
Walsall, who had already hit the bar through a Craig Westcarr free-kick in the ninth minute, had earlier been indebted to goalkeeper Richard O'Donnell for keeping them on level terms before Butler's strike.
It needed a wonder save from O'Donnell to turn Bakary Sako's 30-yard free-kick over the bar six minutes before the interval.
O'Donnell then came to Walsall's rescue again on the stroke of half-time when he pushed out Kevin Doyle's header from Sako's corner as Wolves crashed to their first league defeat of the season - and lost their 100% home record in the process.
An 85th-minute thunderbolt from Jay Emmanuel-Thomas rescued a point for Bristol City in a 1-1 draw with Shrewsbury Town at Ashton Gate.
The lanky midfielder took aim with his right foot from 25 yards and left Shrews goalkeeper Chris Weale, playing against his former club, clutching at thin air as he celebrated his sixth goal of the campaign in all competitions.
The home side paid for a wretched first half display and were caught hopelessly on the break after 28 minutes when Luke Summerfield fed Curtis Main down the right and his low cross created a tap-in for Jon Taylor.
City failed to create a worthwhile chance in the opening 45 minutes and were booed off at the interval. They improved after the break and substitute Marlon Harewood hit the angle of post and crossbar with a 62nd-minute header.
Sam Baldock had forced a flying save from Weale soon after the interval, but Shrewsbury defended strongly and continued to threaten on the break.
The result left Sean O'Driscoll's City still without a League One win this season following relegation in May.
- Sports & Recreation
- Andy Butler
- Bartosz Bialkowski