Bruce Lietzke and Graham Marsh share second place after posting rounds of 5-under-par 66. Dave Eichelberger is one stroke further back at minus-4.
Mark Johnson, the defending champion, opened with a 3-under-par 68. He was joined in fifth place by Peter Jacobsen among others.
Eastwood, a two-time winner in the 1997 season, collected his first birdie at the par-5 third after he chipped his third to 6 feet. He came back with birdies on five and seven to get to 3 under at Newport Beach Country Club.
The 60-year-old stumbled to a three-putt bogey on the par-3 eighth. Eastwood bounced right back with a 12-foot birdie putt on No. 9. He birdied the 12th to move to minus-4.
Eastwood made it two straight as he kicked in a 2-foot birdie putt at the 13th. He parred four holes in a row before a chip-in birdie on the par-5 18th gave him the outright lead.
'I hit lots of good shots. I had seven birdies today and actually thought I made a few more putts,' Eastwood said. 'I just switched irons and switched putters before this week.'
Marsh opened with a birdie on the first. He ran home back-to-back birdie putts from the fourth to climb to 3 under.
The six-time winner on the Champions Tour parred his next four holes before a bogey on the 10th. Marsh got that stroke back with a birdie at 14. He made it two straight with a birdie on the 15th. Marsh birdied the par-3 17th to get to 5 under.
'I got off to a fast start and that's the key to this score,' Marsh said. 'The nature of this course is there is no safe lead.'
Lietzke was steady throughout his round. He got things going with a birdie on the par-4 first. The seven-time winner on the Champions Tour picked up his second birdie on the fifth.
The 54-year-old moved up the leaderboard on the back nine with birdies at 10 and 12. Lietzke tied Marsh at minus-five with a birdie on the 14th. He closed with four straight pars to end there.
Jacobsen and Johnson were joined in fifth place at minus-3 by ACE Group Classic runner-up Brad Bryant, David Eger, Vicente Fernandez, Walter Hall, Joe Inman, Tom Purtzer, Bobby Wadkins and Lanny Wadkins.
Tour ironman Dana Quigley carded a 2-under-par 70 to share 15th place with five other players.