Stokes - who scored a pulsating knock of 161 against Worcestershire last week - picked up from where he left off although he missed out on another century by 18 runs.
Keegan Petersen was also in solid form with an innings of 78 but Durham - the hosts - were bowled out before the end of play on 311.
Michael Hogan delivered with the ball for the Welsh outfit, claiming figures of four for 67, including the key wicket of Stokes to keep Durham in check.
Two late strikes from Matthew Potts began a fightback, leaving Glamorgan with work ahead of them on day two on 31 for two, with Marnus Labuschagne unbeaten overnight on 16.
Glamorgan won the toss and elected to field, facing the leading run-scorer in the County Championship heading into the contest, Sean Dickson.
However, the opener only added five runs to his total before Michael Neser found his outside edge and Sam Northeast clung on at second slip.
Alex Lees and Petersen responded against the new ball by building a solid foundation with a stand worth 62.
Lees appeared on the brink of another score of fifty after driving David Lloyd to the fence, but then chopped on from the following delivery to fall for 44.
After lunch, Scott Borthwick and David Bedingham fell cheaply for the home side to Hogan and Andy Gorvin respectively, but Petersen worked his way past fifty for the second innings in a row.
The South African was fortunate on two occasions against Neser, edging a bouncer between Chris Cooke and Andrew Salter at first slip and seeing a top edge land safely.
Petersen looked to have come through a tough period, but he then presented Lloyd with his second wicket as he played a loose drive that landed in the hands of Labuschagne.
Stokes made a measured start to his innings, but, after the departure of Petersen, he began to free his arms.
His first signal of intent came with an element of fortune against his Ashes rival Labuschagne, edging his medium pace over the slips.
The left-hander then found his range with two crisp strikes to the fence against Lloyd, scattering the Glamorgan fields to the ropes.
The England captain brought up his half-century from 74 balls, sedate compared to his exploits against Worcestershire.
However, he soon delighted the Riverside crowd by dispatching Labuschagne over the leg-side boundary with his first six of the innings, bringing up the Durham 250 in the process.
A promising partnership of 61 between Stokes and Ben Raine allowed the hosts to push towards 300 at speed.
Raine matched the intensity of his team-mate at the other end before Salter turned one through the gate, earning revenge after being struck for 10 from the first five balls of the 79th over.
One wicket quickly brought a second as Hogan secured the vital scalp of the England captain with the new ball with a rising delivery that Stokes could only fend behind to Cooke for 82.
Hogan then wrapped up the tail with two further strikes, but only after Durham scrambled past the 300-run mark to secure a third batting bonus point.
Potts responded for the hosts by taking two wickets to remove Salter and Govrin to swing momentum back in their favour before stumps.