Andrade reeled off five birdies in a row on his way to a seven-under-par 63. Nobody else shot better than three-under 67 at Minnehaha Country Club.
Andrade started his round on the back nine and birdied the par-5 12th before his five-birdie run began at the par-4 14th. He made the turn in six-under 30 and moved to seven under on the second hole, his 11th of the day, before cooling off and making seven straight pars to finish.
"I think it's the best 18 holes I've played on the Champions Tour in my 11 years," Andrade said. "It's been a while and I've had some good scores over the years, but nothing this low in these kinds of conditions."
Andrade won three times on the PGA Tour Champions in 2015 and hasn't earned a trophy since. Not that he's too concerned about turning his headstart into a victory.
"I'm 60 years old. I don't think anyone really cares how I back up tomorrow from today or the next day or next week," Andrade said.
"We're all out here just having a blast, having a great time. And I haven't won in a long time, so it would be so sweet to get back in the winner's circle. So that's all I'm thinking about is going out tomorrow and having a great time with a couple of great golfers."
Four players are tied for second - Steve Stricker, Ken Tanigawa and Australians Steve Allan and Michael Wright.
Allan had six birdies and three bogeys, while Wright began with a double bogey on the par-three 10th before finishing with four birdies on his back nine to get to three under.
Stricker is the two-time defending champion of this event and has three Sanford International titles among his 17 career wins on the PGA Tour Champions. On Friday, he paired five birdies with two bogeys.
Stricker knew Andrade had left the field in the dust.
"I said that going down 17 to the guys in our group, 'That's a hell of a round today,' seven under, a four-shot lead. When you can beat the field or anybody else by four shots in a round, you know you did something special," Stricker said.
Tied for sixth at two-under 68 are Harrison Frazar, South Korean Charlie Wi and Australian Richard Green.
Green had an eventful round, mixed four bogeys with four birdies and a two on the par-four 15th.
Countryman Rod Pampling opened with a 69 and is tied ninth, one ahead of Greg Chalmers, Stuart Appleby and Mathew Goggin.
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