Strange, who opened with a 63 to take a one-shot lead on Thursday, was at 13-under-par 129 overall.
Benn Barham fired a 7-under 64 and climbed into a tie for second place with Robert Dinwiddie (65), Jeev Milkha Singh (68) and Alvaro Velasco (68) at 9-under 133.
Rafa Echenique (67), Raphael Jacquelin (68), Ross McGowan (68), Edoardo Molinari (70) and 2006 champion Robert Karlsson (67) were the only other players within five shots of Strange's lead. They each stood at 8-under 134.
Colin Montgomerie (5 under) and Darren Clarke (4 under) had their work cut out for them, while reigning British Open champion Padraig Harrington, playing in his first Wales Open, missed the 1-under cut line by three shots.
Strange followed his stunning 63 in the first round with a flawless effort on Friday that included five birdies and 13 pars. The 31-year-old Australian said he wasn't used to the soggy conditions players faced in the second round.
'But I guess you just have to try to adapt to what you've got,' said Strange, a two-time winner on the Asian Tour who is seeking his first victory on the European Tour.
'Playing here is different than playing in Asia,' he said. 'It's a lot cooler and there's more moisture in the grass, but I'm adapting quite well.'
Strange birdied four of his first nine holes to keep the lead, then protected it with one birdie and eight pars the rest of the way. His 129 total was five shots better than his previous best 36-hole score this season.
It all had Strange looking forward to winning on the European Tour for the first time.
'It's going to have to happen and you have to learn to deal with it and come Sunday, if you've sort of been around it enough and know how to deal with it, you'll have a better chance of pulling one off,' said Strange.
Paul McGinley, Bradley Dredge and Paul Lawrie were among the players who joined Harrington in missing the cut.
Only four Welshmen moved on to the weekend: Jamie Donaldson, Kyron Sullivan, Garry Houston and Phillip Price. Dredge was among the 13 more who missed the cut.