Graeme McDowell, the leader after round one, and David Howell, who held the top spot through 36 holes, joined Ian Poulter in a tie for second at 15-under-par 201. Scotland's own Stephen Gallacher was one shot further back at 14-under-par 202.
Donald, who has been one of the hottest players on the European Tour with a pair of victories since rejoining the circuit earlier this year, got a chance at Carnoustie, one of the three courses used over the first three rounds. He jumped out of the gate with a birdie at the first and added a birdie at the fourth to take the lead at 15 under.
'You really have to think your way around here, especially this course,' said Donald. 'I think it's the toughest one of the three.'
The 26-year-old holed a crucial putt to save par at the sixth but found trouble a couple of holes later with a bogey at the par-4 ninth.
Donald recovered on the inward half and hit his approach to 20 feet for a birdie at the par-4 10th. Donald then drained a 12-footer for a birdie at the 12th and tallied another birdie at the 14th to extend his advantage.
'It's been unbelievable to come over here and win twice,' said Donald. 'When you're swinging well you don't see trouble. So far so good.'
McDowell played Kingsbarns on Saturday and took advantage early with a birdie at the opening hole after his second shot stopped within 6 feet of the cup. The Ulsterman then converted an 8-foot putt for a birdie at the third and landed his approach inside 5 feet for a birdie at the fourth.
The Ulsterman struggled to a bogey at the eighth but he countered with a birdie at the very next hole. McDowell found trouble again with a bogey at the 13th, but he was not ready to let Donald distance himself completely.
McDowell birdied three in a row from the 14th for a round of 67 in search of his second victory of the season.
'Today was back to business as usual,' said McDowell. 'I've been holing putts all week and making a lot of birdies which is a lot of fun.'
Howell grabbed the second-round lead with back-to-back 65s, but Carnoustie was not as kind to the Englishman on Saturday.
He stumbled to a bogey at the third, but recovered momentarily with a 25-foot birdie at the fourth. Howell found trouble again with a double bogey at the fifth, but he fought hard to stay in control at the sixth and hit out of a bunker to 6 feet for his second birdie of the day.
Howell was also unwilling to let Donald pull away and collected a pair of birdies on the back side for a round of 71.
'I'm delighted and I'm looking forward to tomorrow,' said Howell. 'I'm hitting the ball well.'
Poulter, who teamed with Donald and Howell on the victorious European Ryder Cup team at Oakland Hills last month, mixed three birdies with a bogey over his first nine holes.
The Englishman then torched the back nine with five birdies for a 65.
Gallacher shot a 66 at St. Andrews, where the final round will be contested on Sunday, to finish three shots back.
World No. 2 Ernie Els carded his third straight round of 68 to join Angel Cabrera, John Bickerton and Marcus Fraser in a tie for sixth at 12-under-par 204.
Defending champion Lee Westwood was one shot further back at 11-under-par 205 along with Ian Woosnam, Peter Senior, Fred Couples, Rolf Muntz and Mark Foster.
Vijay Singh, the top-ranked player in the world, posted a 69 to finish in a group at 9-under-par 207.
The 54-hole cut fell at 4-under-par 212 with 73 players surviving for the final round. Among the unfortunate were Padraig Harrington and Paul Lawrie, both former champions of this event.