Blair and Fishburn lead McIlroy and Lowry heading into final round of Zurich Classic
The pair shot a superb 12-under-par 60 to sit at 23-under after the better-ball round to gain the advantage over Luke List and Henrik Norlander heading into Sunday's final round, which will use the alternate shot format.
But the Irish pairing of Rory McIlroy and Shane Lowry are just two shots off the lead alongside the American team of Ryan Brehm and Mark Hubbard.
Blair and Fishburn made an outstanding start with a birdie on the first followed by an eagle on the par-5 second and they kept up their low scoring to reach the turn at 7-under.
Five more birdies followed on the back nine, including a streak of three from the 13th hole onwards, as the pair grabbed the solo lead.
Blair and Fishburn have been playing together since their junior golf days in Utah and are relishing the chance to compete as a pair.
"We go back a long ways and we spent a lot of time together and it's cool to be playing well on the PGA Tour on this stage. This is pretty special," said Fishburn.
"We'll just kind of continue how we're doing. No reason to change anything. We'll just keep having fun and keeping it loose and see what we can do."
Seattle-born List and Swede Norlander have no such long history but both live in Augusta, Georgia.
Their 10-under round of 62 was highlighted by eagles on the par-five second and 11th holes.
World number two McIlroy and his Ireland Olympic and Ryder Cup Europe teammate Lowry remain in firm contention for Sunday's title bid after an eight-under-par 64.
They were boosted by a strong back nine with five birdies, including on the 18th, which left McIlroy looking forward to Sunday's round.
"I can't wait. I think to make those birdies coming in and to only be two behind, alternate shot is a tough format, and you want to be within a couple strokes of the lead. I thought it was important to finish the way we did and excited to have a chance to win tomorrow," said the Northern Irishman.
"It was a tough day. Birdies were a little harder to come by today than they were on Thursday in the better ball format.
"I think today was about staying patient knowing that the course was going to present some opportunities, especially on that back nine, and I think our patience was rewarded with the chances that we gave ourselves, and rolled a couple of putts in on the back and kept ourselves in it."