Knox, the world No 23, suffered the fate for the second year running while 1988 winner Lyle has now bowed out early three times in a row.
It was a case of too little, too late for Knox as the Scottish No 1 fell two shots short, having missed out by the same margin on his debut 12 months ago.
The 31-year-old, who’d opened with a four-over 76, was seven-over for the round when he made his first birdie of the day at the 15th before following that with a 2 at the next hole.
He then chipped in to save par at the 17th and almost holed out for an eagle-2 at the last with a 6-iron from 178 yards. His third birdie in four holes gave him another 76.
“I had no magic, I guess, for the first 68 holes,” Knox told The Scotsman afterwards. “Luck’s not the right word. Nothing got going. I just wasn’t good enough, I guess.
“It was nice to finish well and I was standing over my second shot at the last thinking, ‘maybe if I hole out here’.”
Alas, the damage had already been done, having gone out in 40, four-over, before spilling three shots in a row from the 12th.
“I’m bummed. I’m disappointed,” he groaned. “My putter let me down again. My putting was just horrific.
“The course is playing so that difficult and I just wan’t able to get any momentum going.
“I had so many chances for birdie or par to get things going, but I couldn’t make anything.”
He refused to blame the tough conditions, adding: “Last year was windy as well for the first two rounds.
“I didn’t play poorly. There was so many shots that I was a couple of yards out from being good. Flying the green at three, for instance. The same at both 9 and 14, where I came up a yard shot each time.
“They all cost me shots whereas if they’d been a couple of yards more I might have made birdie. There’s the difference between missing the cut and being in the tournament.”
Making his 36th appearance, Lyle ran up a quintuple-bogey 9 at the 11th as he carded an 83 - his worst score here since an opening 86 in 2012.
“It was a horror story,” declared the 59-year-old afterwards. “It was a poor tee shot, a semi-shank back into the trees, chip out then I put it into the water with whatever it was - my fifth shot, I think - and, just like that, it was a 9.”
He was bitterly disappointed to make just one birdie in 36 holes, adding: “That’s killed me and it was my driving that cost me more than anything else over the last two days.
“I drove it really well last year and I was never under pressure. This year I had four or five errant ones that put me in the wrong place at the wrong time.”
Lyle, who’d come home in 41 on Thursday for an opening 77, started his second round with three straight pars before stumbling to four successive birdies.
“It was always going to be a struggle,” he admitted. “I thought I could maybe get it round in 72 or 73 today, but it all started to go a bit flat after a reasonably solid start.”