The team changes suggested the home side would be favourites, but not the scale of the one-sided encounter that followed.
Middlesex recalled Roland-Jones for Jack Nelson, while Glamorgan gave debuts to two seamers – 18 year old academy product Tom Edwards and Aussie Connor O’Riordan, who has been on an extended second team trial.
Both teams have five players at the Hundred, but Glamorgan also chose to rest the overworked Timm van der Gugten as well as veterans Colin Ingram and Chris Cooke, with Zain ul Hassan on paternity leave, teenage prodigy Tom Norton missing at least most of the competition with a back issue, Jamie McIlroy suffering a minor niggle, and Billy Root not selected.
Sharma was quickly into his stride having Callum Nicholls adjudged lbw, but with Byrom getting the ball away for six fours, Glamorgan got to 44 before they fell apart, losing wickets in six consecutive overs.
Sharma had Henry Hurle (10) caught by keeper Joe Cracknell, Jack Hope-Bell caught to mid-off and Will Smale given lbw.
Meanwhile Roland-Jones induced Byrom (29) and Dan Douthwaite to edge to slip, Sam Robson snaffling two smart grabs, while Alex Horton feathered a catch behind.
Roland-Jones bowled his 10 over allocation straight through, while Sharma was replaced after seven by Cornwell, who wrapped up the last three while Cracknell finished with four catches.
The difficult bounce did not excuse the extent of Glamorgan’s struggles against an accurate seam attack.
With 20 coming off a nervous first over from O’Riordan, Josh de Caires got Middlesex off to a flyer.
Captain Andy Gorvin took himself off after just two overs just to give Edwards a bowl, but the 50 came up in just six overs as De Caires and Nathan Fernandes were able to attack with freedom.
Fernandes (14) drove Edwards to mid-on to give the youngster a first senior wicket, and a second quickly followed when Sam Robson was caught behind.
But De Caires (45 not out off 30) hit the winning run off the first ball of the 10th over to complete the rout.
Middlesex next travel to Worcester on Friday 31 July.
Glamorgan are set to come up against former England captain Ben Stokes at Durham on Wednesday, with further away fixtures against Derbyshire and Hampshire to follow as they try to rebuild confidence.