Batsman David Lloyd struck a career-best 119 to put Glamorgan in control at Bristol, with Gloucestershire still 157 runs short of avoiding an innings defeat and already five wickets down.
Lloyd started cautiously, but accelerated as his innings progressed, hitting 18 fours and a six as he put on 117 with Marchant de Lange, who registered his maiden half-century for Glamorgan, before the Welsh county declared on 526-9.
Lukas Carey then dismissed both openers for the second time in the match, before de Lange took three more wickets to take his match tally to eight.
"It's very pleasing for myself to start the season well and put the team into a good situation, it was a great day and hopefully we can cap it off with a win, but we'll have to work hard and stay patient," said David Lloyd.
"Last season it was filling a role for the team (at three), it was nice to start the season with a hundred (in the middle order) and hopefully I can keep on scoring big runs throughout the season, I've been working through the winter to be mentally stronger."