Scott Stallings birdied the final hole to take a one-stroke lead after the first round of the Memorial at Muirfield Village.
Stallings made one of only four birdies at the 18th to finish with a six-under 66 - a shot ahead of double heart transplant patient Eric Compton and Spencer Levin.
A pack of seven players sat two shots further back, including Brandt Snedeker and Aaron Baddeley, after 69s.
"We've got a long way to go," Stallings, who fired three birdies in the final four holes, said.
"I was happy to get a good round under par. I haven't had a round under par since Saturday at Augusta. It's been a long time."
But Phil Mickelson endured a miserable day, carding a seven-over-par 79 and subsequently withdrawing from the tournament, citing fatigue.
The American world No 12 pulled out of the elite event hosted by Jack Nicklaus at Muirfield Village Golf Club after covering his back nine in six-over 42.
"I think mentally I'm a little bit fatigued," Mickelson told reporters. "The course here is in such great shape. It's a beautiful way to get ready for the US Open.
"But I'm hitting it so poorly ... I have to look at what's best for me to play in the US Open, and I'm going to take the next few days to kind of rest up."
The US Open, the second of the year's four majors, will be played from 14-17 June at San Francisco's Olympic Club.
Collated first round scores in the USPGA Tour the Memorial Tournament presented by Nationwide Insurance, Muirfield Village GC, Dublin, Ohio, United States of America
(USA unless stated, par 72):
66 Scott Stallings (USA)
67 Spencer Levin (USA), Erik Compton (USA)
69 Aaron Baddeley (Aus), Rory Sabbatini (Rsa), Matthew Every (USA), Andres Romero (Arg), Brandt Snedeker (USA), Daniel Summerhays (USA), Blake Adams (USA)
70 Bud Cauley (USA), Tiger Woods (USA), Adam Scott (Aus), David Hearn (Can), Ben Curtis (USA), Scott Piercy (USA), Mark Wilson (USA), Ernie Els (Rsa), Ryan Moore (USA)
71 Robert Garrigus (USA), Greg Chalmers (Aus), Stewart Cink (USA), Geoff Ogilvy (Aus), Harris English (USA), Dustin Johnson (USA), Charlie Wi (Kor), Rory McIlroy (Nirl), Trevor Immelman (Rsa), Kyle Reifers (USA), David Mathis (USA), John Huh (Kor), Luke Donald (Eng), Jonathan Byrd (USA), Rickie Fowler (USA)
72 Seung-yul Noh (Kor), Jeff Overton (USA), Greg Owen (Eng), Ben Crane (USA), Vijay Singh (Fij), Marc Leishman (Aus), Jimmy Walker (USA), Rodney Pampling (Aus), Nicolas Colsaerts (Bel), Ryo Ishikawa (Jpn), Ricky Barnes (USA), Brendan Steele (USA), Hunter Mahan (USA), George McNeill (USA), J.B. Holmes (USA), Kevin Stadler (USA), Jim Furyk (USA), Johnson Wagner (USA), Troy Matteson (USA), Cameron Tringale (USA)
73 Nick Watney (USA), Steve Stricker (USA), Brian Davis (Eng), Brendon De Jonge (USA), Charl Schwartzel (Rsa), Chris Di Marco (USA), Kelly Kraft (USA), James Driscoll (USA), Kevin Streelman (USA), Justin Rose (Eng), Robert Allenby (Aus), Bill Haas (USA), Brandt Jobe (USA), Bo Van Pelt (USA), Camilo Villegas (Col)
74 Pat Perez (USA), Chris Stroud (USA), Martin Flores (USA), Lucas Glover (USA), Davis Love III (USA), Billy Mayfair (USA), Branden Grace (Rsa), Will Claxton (USA), Nick O'Hern (Aus), Kevin Chappell (USA), Jonas Blixt (Swe), Fred Couples (USA), Jason Day (Aus), Michael Thompson (USA), Steve Marino (USA), K J Choi (Kor), Jhonattan Vegas (Ven), Henrik Stenson (Swe)
75 Jerry Kelly (USA), Bryce Molder (USA), Chris Kirk (USA), Charley Hoffman (USA), Kyle Stanley (USA), Louis Oosthuizen (Rsa), Bubba Watson (USA), Chris Couch (USA), Angel Cabrera (Arg), Ryuji Imada (Jpn), Ken Duke (USA)
76 D.A. Points (USA), Keegan Bradley (USA), Kevin Na (USA), Kris Blanks (USA), Carl Pettersson (Swe), J.J Killeen (USA)
77 Garth Mulroy (Rsa), John Senden (Aus), Gary Woodland (USA), Brian Harman (USA), Stuart Appleby (Aus)
78 Colt Knost (USA), Webb Simpson (USA)
79 Phil Mickelson (USA), Sang-moon Bae (Kor), Bryden Macpherson (Aus), Tommy Gainey (USA)
80 Bo Hoag (USA)
81 Tom Gillis (USA)
82 Boo Weekley (USA)
83 Mike Weir (Can)
84 Billy Hurley III (USA)