Rose fired a 6-under 64 on Friday, taking advantage of being in a morning wave that saw less wind than the afternoon players.
"Really good days' work today," said Rose, the Englishman who won the 2013 U.S. Open and is ranked fifth in the world.
"I played well. I was happy with my game. I hit it really good off the tee for the most part. Able to capitalize with some iron play and make just enough putts."
Rose, who will tee off at 1 p.m. with Emiliano Grillo (9-under), has to feel good about his chances going into the weekend even though he hasn’t played this event since 2010. But other top players aren’t far behind.
Brooks Koepka, the reigning U.S. Open champion, is tied for third at 7-under after posting a 7-under 63. He feels about where he did a year ago at this time, and is eyeing a win in his first Colonial appearance.
"Feel like we’ve got a good game plan on this golf course," said Koepka, who tees off with Satoshi Kodaira at 12:50 p.m. “We’re executing quite well. It’s something that’s been coming. I feel like we’re ready to win."
Japan’s Kodaira, a top-30 player who is also at 7-under, and Grillo, a 25-year-old from Argentina who has one PGA Tour win, are also right in the mix.
A couple other big names within striking distance are Rickie Fowler, at 4-under and six shots off the lead after two sub-par rounds, and Jordan Spieth, the hometown favorite and 2016 event winner who stands seven shots back at 3-under.
Spieth, No. 3 in the world, tees off at 10:30 a.m. with another past Colonial champion, Steve Stricker. Fowler is paired with Tom Lovelady for an 11:30 a.m. tee time.
Spieth and Fowler were among those players in the afternoon wave when the wind picked up.
Bryson DeChambeau estimated scores were at least two strokes higher in the afternoon because of the wind.
"The wind was treacherous out there today. It was switching everywhere," said DeChambeau, the SMU product who is tied for sixth at 5-under.
"Got cooler, which was nice, but I’d rather have the hotness and no wind."
A few notable names won’t be playing on the weekend.
Two-time Colonial champion Zach Johnson missed the cut for the first time in his career, going 6-over through the first two days. Also missing will be Jason Dufner, who has two runner-up finishes in the event.
Xander Schauffele started the tournament with four straight birdies, but missed the cut after posting consecutive rounds of 72. Aaron Wise, who won last week's AT&T Byron Nelson, also missed the cut, along with Webb Simpson, this year’s Players champion and the 2012 U.S. Open winner.
But this remains a strong field with, fittingly, one of the top players in the world – Rose – in position to win it going into the weekend.
"Not going to stress about it," Rose said. "Going to have a late tee time tomorrow; going to be playing in the heat. For me, it’s all about resting up, getting rehydrated and coming out strong."