Wiebe fired a season-best 7-under-par 65 to take a one-shot lead over Davis Love III and Phil Mickelson.
Tiger Woods is eight off the pace following a double bogey at the par-4 18th.
The 1997 and 1999 Western Open champion didnt record his first birdie until the 14th hole. One-under through 17 holes, Tiger dumped his second shot into the pond left of the 18th green.
He had no comment after his round of 1-over-par 73.
Mickelson is fresh off his second win of the season at the Canon Greater Hartford Open. Seemingly always in contention ' he has nine top-3 finishes this season ' Mickelson once again moved near the top of the leaderboard by posting a bogey-free 66.
The goal is not to get way up the leaderboard in the first three rounds. The goal is to try and get into contention by Sunday, said Mickelson.
Wiebe hasnt been in contention in quite some time. He kick-started the season with a tie for fifth in the Touchstone Energy Tucson Open; however, in 13 starts since he has yet to record another top-10.
This could prove to be the biggest event of the season for the 43-year-old. The two-time Tour winner isnt exempt for this years British Open; though he could gain entrance to Royal Lytham should he finish among the top eight this week who arent already eligible for the Open Championship.
This is a big tournament for anyone, but this can get (me) into the British Open and Ive been looking forward to it for a couple of weeks, said Wiebe.
Winless since 1986, Wiebe carded seven birdies to no bogeys on Thursday.
I wanted a good start and, of course, I want a good ending; but a good ending is easier with a good start, he said.
Love got off to a horrendous start last week; going triple bogey, double bogey en route to an opening 77 at in Hartford.
Such was not the case this week.
Starting at the 10th on the Dubsdread Course, Love birdied three of his first four holes before dropping a shot at the par-3 14th.
He birdied the 15th and 16th holes to make the turn in 4-under-par 32, and then added birdies at the 1st, 5th and 7th holes to take a two-shot advantage over the field at 7-under.
However, Love closed his scoring with a bogey-5 at the 8th.
Love almost skipped this weeks event, but after his dismal performance in Connecticut he made a late commitment to the Western.
Thanks to a nagging back injury, Love is making just his third start since the WorldCom Classic in mid-April.
Hes now being advised to play, and play often.
I dont need to play six weeks in a row, but I need to play a lot of golf, said Love. I was told before Hartford to try and go play everyday, whether it was on Tour or at home, build my stamina back up, get back used to hitting golf balls everyday.
Full-field scores from the Advil Western Open