Lancashire's England seamer James Anderson took three wickets but Glamorgan had the better of their Division Two clash at Colwyn Bay.
Lancashire had opted to bat first after winning the toss on a good-looking Rhos-on-Sea pitch but found themselves bowled out for just 123.
Michael Hogan and John Glover claimed three wickets apiece for the hosts.
In reply Glamorgan reached 110-4 by the close, a deficit of 13, with left-handers Will Bragg and Marcus North proving the mainstay of the home effort with a partnership of 46 as Anderson took 3-28 from 15 overs.
Australian Hogan set the tone for Lancashire's demise by bowling Paul Horton, who offered no shot, with the second ball of the match, and Lancashire were quickly reduced to 66-5.
Hogan continued his fine new ball spell by also bowling Karl Brown, while top-scorer Luke Proctor (26) was trapped leg before by all-rounder Jim Allenby before, in the next over, Mike Reed claimed the prized wicket of Ashwell Prince, who also went lbw for 17.
Simon Katich and Gareth Cross steadied the ship briefly, taking Lancashire to lunch at 86-5, but both batsmen were dismissed by Glover, in the side for the injured Graham Wagg, in the space of five balls after the interval.
Anderson had reached double figures before the innings was brought to a close by the second ball of off-spin from North, who snared Simon Kerrigan for seven.
Glamorgan began their reply patiently but Anderson accounted for both Ben Wright, who went shortly after tea for six, edging a lifting delivery behind, and Stewart Walters, who was bowled for 15 attempting to force the ball onto the legside.
North and Bragg did well in the evening session until the day's top scorer, Bragg, went lbw to a quicker ball from slow left-armer Kerrigan's fourth ball for 34. Two overs later Anderson struck again to have North leg before for 22.