Suber carded a five-under-par 65 to move one shot clear of England's Daniel Brown and South Korea's Im Sung-jae after an impressive first appearance at golf's oldest major.
The 26-year-old, ranked 115th in the world, was level par through nine holes before catching fire on the inward half. He picked up five shots over the next eight holes, highlighted by an eagle at the 17th.
The opening round was even more remarkable considering Suber had never played links golf before arriving in Europe this week.
"Monday was my first round of links golf, so I've played 27 holes before I played the first round today. I've never been to Europe," Suber said.
"Things just really started going after the birdie on 10. I just felt like the momentum was really in my favour."
Scheffler opened with a steady two-under-par 68 to stay firmly in contention despite missing several chances to climb higher up the leaderboard.
The defending champion made four birdies in five holes early in his round before bogeys at the seventh and 17th slowed his progress. He also narrowly missed a birdie at the last after his putt stopped just short of the hole.
"I got off to a hot start in the round today and wasn't able to make as many birdies as I would have hoped to down the stretch," Scheffler said.
"If I continue to strike the ball the way I did today and just keep giving myself looks, that's part of it. Golf is played over 72 holes, and I definitely liked what I saw today."
Bryson DeChambeau also made a strong start with a three-under-par 67 as he looks to avoid a fourth straight missed cut in a major this season.
The two-time US Open champion has often struggled in links conditions but was pleased with his opening performance.
"There's still a lot of golf to be played, but, ultimately from my perspective, I was really excited about the way I played," DeChambeau said.
World number four Cameron Young also finished on three under to remain well placed heading into Friday.
Rory McIlroy, however, has work to do after an erratic two-over-par 72 left his hopes of lifting the Claret Jug under pressure.
The Northern Irishman struggled in worsening afternoon conditions, dropping six shots during a frustrating round that included bogeys on both par fives.
McIlroy now faces a battle to make the cut and keep alive his bid to win The Open for the first time in 12 years.
England's Matt Fitzpatrick also finished on two over after finding it difficult to build momentum.
Local favourite Tommy Fleetwood ended with a one-under-par 69 after birdies in two of his final four holes kept him in touch with the leaders.
Bryson DeChambeau and defending champion Scottie Scheffler made encouraging starts to The 154th Open, while Rory McIlroy faces work to do after a disappointing opening round.
The 154th Open Championship got underway under clear skies at Royal Birkdale in Southport on Thursday, with World No 1 Scottie Scheffler beginning his bid to become the first player in 17 years to successfully defend the Claret Jug.
Six-time major champion Rory McIlroy is ready to test his mettle at this week's 154th Open Championship at Royal Birkdale.
Rory McIlroy held on to a share of the Scottish Open lead on Friday, joining Tom Kim and Jordan Smith at the top of the leaderboard after the second round at The Renaissance Club in North Berwick, Scotland.
