The visitors needed just five wickets on the final day to complete an impressive win as Lancashire resumed on 39 for five - with a victory target of 328 all but forgotten - and Samit Patel claimed the final two scalps as Lancashire were all out for 142.
Andre Adams and Stuart Broad finished with three wickets apiece, while Graeme Swann chipped in with two.
Luke Proctor struck six fours in his 41 not out, while Glen Chapple also contributed 26 to put up some form of resistance for the Red Rose, who fell to their third defeat of the season.
Joe Denly's first century for
Denly, who moved to London from Kent over the winter, made an unbeaten 134 as Middlesex declared on 327 for seven, with veteran seamer Alan Richardson continuing his amazing early season form after claiming five for 89.
In response, Tim Murtagh and Toby Roland-Jones took the wickets of openers Daryl Mitchell and Michael Klinger respectively as Worcestershire closed on 45 for two.
In Division Two, Matt Boyce's highest first-class score was not enough to prevent
Opener Boyce's 122, three runs more than his previous best of 119 made against Gloucestershire last summer, along with knocks of 69 and 67 from Josh Cobb and Wayne White respectively frustrated Yorkshire.
However, Leicestershire were eventually all out for 309 following-on, with Steve Patterson taking five for 77 to finish with career-best match figures of eight for 94.
David Willey's five-wicket haul inspired
Set 297 runs to win after Northants declared on 232 for nine, Hampshire were all out for 179, with Willey claiming five for 39, including the wicket of Michael Carberry, who top-scored for the visitors with 61 before he was trapped in front.
Despite Charl Willoughby's best efforts,
Essex declared on 166 for nine to leave the hosts chasing 239 on the final afternoon, but despite Willoughby taking four wickets, they shook hands with Glamorgan on 99 for five.
There was also a stalemate at Derby, where
Hamish Marshall 10 runs shy of a century, but Ian Cockbain's unbeaten 63 ensured their would be no collapse.