The win comes one day after the A's lost 22-9 at Yankee Stadium, allowing a major league-record three grand slams.
Dustin Pedroia and David Ortiz hit consecutive homers for Boston, which opened a nine-game homestand after going 6-2 on a recent trip through Texas and Kansas City.
Wakefield (6-6), making his sixth try to become the 108th pitcher to reach 200 wins, gave up eight runs — four earned — on eight hits, walking two and striking out three. He's 0-3 with a 4.97 ERA during the six games.
Jemile Weeks and Cliff Pennington each had three hits, and Willingham drove in four runs for the Athletics, who won for the seventh time in nine road games after losing 30 of their previous 37 away from home.
Gio Gonzalez (11-11) gave up four runs and seven hits while striking out five and walking three in 5 2/3 innings for his second straight win after losing five in a row. He picked up just his third road win in 10 decisions.
Leading 2-1 in the fourth, the Athletics scored six runs off Wakefield — four coming after Jarrod Saltalamacchia's passed ball on Weeks' strikeout with two outs.
Sizemore started the scoring with a home run into the last row of Green Monster seats in left, making it 4-1. After Weeks fanned but reached first, Coco Crisp walked before Hideki Matsui doubled both home with a drive off the center-field wall. Willingham then homered into the Monster seats, his 23rd, making it 8-1.
Boston outfielder Darnell McDonald pitched the ninth, allowing Willingham's two-run double after walking the first two batters.
For a while it looked as though it could be similar to Thursday afternoon in New York when Oakland opened a 7-1 lead before its pitching staff was pounded.
Boston answered with a pair of runs in the bottom of the fourth on consecutive homers by Pedroia and Ortiz. Pedroia's was his 17th, tying his career high set in 2008 when he won the AL's MVP award. Jacoby Ellsbury tripled and scored.
The Red Sox had runners on first and second with one out in the sixth, but Gonzalez got McDonald to pop to second. Brian Fuentes relieved and Ellsbury fouled weakly to third. Boston stranded two more in the seventh.
Oakland ended any likelihood of a comeback by scoring four in the eighth against Matt Albers, opening a 13-4 lead.
Boston grabbed a 1-0 lead in the first on Adrian Gonzalez's RBI single before Oakland took the lead with two in the second, coming on RBI singles by David DeJesus and Pennington.
Notes
Red Sox LF Carl Crawford didn't start, getting a night off to rest before playing both ends of Saturday's doubleheader. "He was cramping up a little bit [Thursday]," said manager Terry Francona, who hoped to rest some other players but also knew the club has both Sunday and Monday off after Sunday's afternoon game was moved to Saturday night because of the expected severe weather from Hurricane Irene. … Francona said RF J.D. Drew, on the disabled list with a left shoulder injury, was scheduled to DH for the Class-A Lowell Spinners on Friday night and he's also scheduled — along with Kevin Youkilis, on the DL with a strained lower back – to get some at-bats with Triple-A Pawtucket Tuesday or Wednesday. … Red Sox reliever Bobby Jenks (back) is scheduled to pitch an inning at Class A Salem on Saturday and the hope is he can get in some work at Pawtucket before he returns from his third stint on the DL. … Boston is planning to go with Jon Lester (13-6) in the opener on Saturday against Guillermo Moscoso (6-7), scheduled for a noon start. Erik Bedard (4-9) is slated to face Graham Godfrey (1-1) in the nightcap that's planned for 5 p.m. Godfrey will be recalled from Triple-A Sacramento before the game. He made four starts with the A's earlier this season. … Oakland recalled left-handers Josh Outman and Jerry Blevins from Sacramento before the game, sending Jordan Norberto and Bruce Billings to the Triple-A club.