After two holes, Casey had the lead to himself at Muirfield Village, and that was only the start of another big day. He took advantage of the par 5s for another 6-under 66, giving him a three-shot lead over Masters champion Bubba Watson going into the weekend.
McIlroy, whose 63 was the lowest first round in the 39-year history of the tournament, was barely in the picture. He was 15 shots worse with a 78, courtesy of three straight double bogeys and his fourth straight PGA Tour event with a nine-hole score of 40 or higher. McIlroy went from a three-shot lead to nine shots behind.
''To be honest, I thought I was going to be playing a round to try and maybe catch a couple of guys,'' Casey said. ''I woke up checking the scores to see what Rory was going to be. That's really what I was going to be doing -- see how many under I was going to have to try to shoot to chase. Obviously, that didn't happen.''
Casey, taking another step on a long road back from injuries that nearly derailed his career, was at 12-under 132.
He made his first birdie with his best drive of the day on the par-5 11th, setting up a 4-iron onto the green for a two-putt birdie. He made eagle on the par-5 15th hole for the second straight day, and he stuffed it close around the turn for birdies to start pulling away from the field.
Watson gave him a good run in an active round that featured six birdies, five bogeys and an eagle. He only was angry at a few shots where he failed to concentrate. Even so, a bogey-bogey finish wasn't enough to entirely ruin his day. Watson has never finished better than 23rd in eight previous appearances.
''I can't look at the bogeys,'' Watson said. ''I've got to look at where I'm at. If you told me it's my best two days around this golf course, I'd take it.''
Chris Kirk (70) was four shots behind. Hideki Matsuyama (67) and Martin Flores (68) were five back.
Adam Scott, who won Colonial in his debut at No. 1 in the world, shot 70 and was at 5-under 139, still in the mix depending on how Casey fares on the weekend. Phil Mickelson was happy to get in two more rounds. He shot a 70, though he was 10 shots back.
Casey, once a Ryder Cup regular who reached as high as No. 3 in the world, is slowly getting his game and his life back in the right place. He endured injuries to his shoulder and his toe that kept him winless for more than two years. He went through a divorce. He wondered if he would ever return to the brand of golf he was capable of playing.
Weeks like this offer promise.
Casey won the Irish Open a year ago with what he called ''spectacular'' golf. The game is still there.
''It's slowly crawling along and making progress, climbing back up the ladder, however you want to phrase it,'' Casey said. ''It's very difficult when you've played to a certain level and then ... I genuinely had no clue how to play to that level.
''Luckily, I didn't think about that too long.''
His life is back in order. Casey is married to British television presenter Pollyanna Woodward. They are expecting their first child (a boy) in September. He talks about having perspective, knowing where golf fits on his list of what's important.
His golf has looked familiar over the last two days.
McIlroy could say the same. Except for last week at the BMW PGA Championship in England, which he won with birdies on the last two holes, McIlroy's good golf has been stalled by bad patches, and Friday was no exception.
In fact, it nearly has become the rule.
He shot a 43 on the back nine - he started the round at No. 10 - making this the fourth consecutive PGA Tour event where he shot at least 40 over nine holes. All of them have been in the second round.
McIlroy twice hit the trees on the 13th hole and made double bogey. He hit into the water on the 14th for double bogey. And then he double-hit a wedge on the 15th to make it three straight double bogeys.
''These little runs I'm getting on where it gets away from me, I was able to avoid that last week,'' McIlroy said. ''Not so much this week. Even though I had such a bad day, I'm still in with a chance depending on what the guys do this afternoon. So going into the weekend, not exactly where I want to be. But it could be worse.''
Casey simple made it a lot harder.