Wie reeled off nine birdies in a round which got off to a poor start after a ‘skulled’ lob wedge led to a bogey at the par-5 second.
But that clumsy effort sparked the 2014 US Open champion who hit back with three birdies to the turn before lighting up the back nine with a 6-under 30.
Teeing off just after 7.30am, Wie was among those to get the best of the conditions with afternoon storms causing two delays.
She is one ahead of Korea’s In Kyung Kim and two ahead of fellow American Lindy Duncan, World Number Two Lexi Thompson among a group of five players at 5-under and T4.
For Wie the round is of particular significance after she was forced to withdraw from last month’s US Women’s Open with a neck injury incurred at the Women’s PGA.
However, playing pain free Thursday in Scotland she made the most of the perfect weather.
“I’m really proud of myself and how I played today,” she said after her round.
“We did get the best of the conditions this morning but it was a really fun round. This is a great test of golf, a lot of pot bunkers out there obviously.
“I felt like I struggled a little bit in past British Opens so I made it a point to come to the Scottish Open last week and get some good practice in.
“I felt that really helped me a lot just getting used to playing links golf because it is so different.”
Other noteable performances on the day came from England’s Dame Laura Davies, who had to survive pre-qualifying just to get in the field, who posted a 4-under 68 to be inside the top 10.
Davies was cruising at 6-under through 14 holes but made a double bogey at 15 and compounded it with another bogey at 16 before clawing one shot back with a birdie at the last.
Vic Open winner Mel Reid is also in the mix at 5-under while World Number One So Yeon Ryu battled the late afternoon conditions to return a respectable 1-under 71.
Lydia Ko continues to struggle with her game and recorded two bogeys against a lone birdie for a 1-over 73 which has her in the bottom third of the field.
Brooke Henderson is 2-under and T33 while Ariya Jutanugarn is at 1-under and T50.
Whitney Hillier is the best placed of the Australians at 1-under, a full wrap of their day can be found here.