Youkilis, who moved across the diamond to third base, drove in two runs and scored twice and Casey had two hits and three RBIs on Thursday night to help the Red Sox forget about Lowell's injury and beat the Detroit Tigers 12-6.
Youkilis also fielded seven chances at third base flawlessly, including all three outs in the first inning, when he made a barehanded grab of Placido Polanco's bouncer.
"Youk put on a show defensively," said Lowell, who went on the 15-day DL with a sprained left thumb before the game. "And they both swung a pretty good bat."
J.D. Drew went 3-for-3 with two runs and two RBIs, and Tim Wakefield fluttered his knuckleball for five innings as the Red Sox supported him with three four-run innings. Each one came after the Tigers scored in the top half.
"That's always a no-no, when you score and you come right back and give them runs," said Detroit manager Jim Leyland, whose team lost for the eighth time in nine games. "That usually spells a long evening and we did that several times -- not only a run, but big runs."
Manny Ramirez had a two-run double and he also scored a run by ignoring a two-handed stop sign put up by third base coach DeMarlo Hale. Casey hit a two-run single in the four-run seventh to give Boston an 8-3 lead, but five straight Detroit batters reached base in the eighth off Julian Tavarez and cut the deficit to 8-6.
"It got a little hairy, and it wasn't very comfortable for me," Red Sox manager Terry Francona said. "When [Tavarez] got that double play, there was nobody happier in the ballpark than me."
The Red Sox added four in the eighth on a two-run double by Youkilis, Drew's sacrifice fly and an RBI single by Coco Crisp. Papelbon pitched a scoreless ninth for his third save in three tries.
The Tigers stranded six baserunners in the first three innings despite failing to get a hit off Wakefield (1-0). He walked five and hit two batters by the time he was done, allowing three hits and one earned run while striking out five to improve to 10-1 in his last 12 starts at Fenway.
Nate Robertson (0-1) allowed eight hits and two walks while striking out six in 5 1/3 innings, giving up all of his four runs in the fourth inning. Five Detroit pitchers combined to throw 212 pitches, allowing 13 hits and nine walks.
"There isn't a bullpen in the history of baseball that could help a team when the starters can only muster five innings every night," Leyland said. "That's where you start, and we'll worry about the bullpen after we get that straightened out."
Detroit's Ivan Rodriguez reached base all five times he came to the plate, with three singles, a walk and a hit-by-pitch.
The crowd of 37,612, boosted by the offseason addition of nearly 1,000 seats, was the most at Fenway since World War II.
The Red Sox celebrated "Japan Night," playing the Japanese national anthem before the game with Japanese dancers and drummers on the warning track. ... Drew has a hit in all seven games in which he's played. ... The Red Sox purchased the contract of Jed Lowrie from Triple-A Pawtucket to replace Lowell. ... Robertson is 1-3 with a 7.36 ERA in four Fenway starts. David Ortiz is just 3-for-22 against him, the worst numbers against any pitcher he has faced more than 20 times. ... Ortiz is in an 0-for-10 slump. He was the only Red Sox starter without a hit.