Wales beat Scotland away from home for the second time in eight months as a dominant first half did the damage at Scotstoun.
It also handed Scotland head coach Philip Doyle his first defeat in three games since taking charge.
Bethan Lewis and Lisa Neumann's early tries set the tone and Wales added a penalty try before the break.
The Welsh rarely looked troubled from then on as they followed up their 15-13 win over Ireland last week.
Scotland head coach Doyle told BBC Alba: "It was a hard day at the office but a lot learned. Wales are very good with the set-pieces and we struggled with that in the first half."
A late converted try had broken Scottish hearts in March as Wales escaped from Scotstoun with a 17-15 win, the closest the home side had come to a positive result as they were whitewashed in the Six Nations.
Lewis repeated her try-scoring exploits of that day as Wales' pack powered them over the line with a rolling maul on 12 minutes.
Nine minutes later, Wales stretched the Scotland backline. Lauren Smyth chipped the ball through to Neumann, who shrugged off Chloe Rollie all too easily to make it 10-0.
Both conversions were missed by Elinor Snowsill, but it appeared to matter little as Wales dominated the home side.
Scotland, looking to follow up on two victories over Springboks Women under Doyle, reduced the arrears to seven.
Rhona Lloyd spun past a red shirt and got the home side forward. Jade Konkel charged through the middle and, as Scotland won a penalty, Helen Nelson sent the kick through the posts to get them off the mark.
But they found themselves 17-3 down at the break after they had repelled sustained Wales pressure on their five metre line. Emma Wassell was shown a yellow card for a side entry into the maul and Wales eventually were awarded a penalty try.
Scotland's Louise McMillan collected a loose pass and raced forward before touching down for what she thought was the hosts' first try of the game. However, her celebrations were cut short when it was ruled that Wales had not been given sufficient advantage from Jenny Maxwell's knock-on.
Sarah Denholm and Evie Tonkin made their Scotland debuts with 15 minutes to go, but a mazy run from Chloe Rollie apart, there was little for the home crowd to cheer.