At 3-under 141, Harrington led Joakim Backstrom (71), Simon Wakefield (72) and Andres Romero (74).
Harrington had five birdies and one bogey to move past four overnight leaders, boosting his chances of becoming the first Irishman to win the tournament since John O'Leary in 1982.
On Thursday, Romero shared the lead at 4-under with Peter Gustafsson, who shot a second-round 75, Peter Hanson (78) and Simon Dyson (78).
Only 11 players broke par at the Adare Manor near Limerick, with most struggling in wind of up to 40 mph. Officials moved some tees up to cut the course length 76 yards to 7,131 yards.
'The wind doesn't bother me,' Harrington said. 'So I know I have an advantage in that sort of weather.'
Harrington said he's motivated to win this tournament.
'This is my national Open,' Harrington said. 'It means a lot to me. I know I want to win this very badly.'
Three players pulled out with back injuries -- Notah Begay, Ian Woosnam and Anton Haig. Mikko Ilonen withdrew with a wrist injury, and three more did not complete their rounds.