Abreu hit his 20th homer and Adam Dunn added a three-run shot as Chicago beat San Francisco 7-6 on Wednesday, handing the Giants their fifth straight loss.
Abreu reached 20 homers in his 58th game, the third fewest in major league history behind Wally Berger (51 games) and Mark McGwire (56 games).
The Cuban first baseman lined an 0-2 offspeed pitch from three-time All-Star Tim Hudson deep into the left-field bullpen for a two-run homer in the first inning .
He's also homered off Cy Young winners David Price, Clayton Kershaw and Justin Verlander so far this year.
"We're happy with what he's doing," manager Robin Ventura said. "He's getting some hits and important RBIs against some great pitchers, so that's a good sign."
Abreu didn't know his 20th homer moved him into elite company.
"I wasn't aware of this happening, but it's a great thing and I welcome it," the 27-year-old said through a translator. "I'm just going to continue to help the team win, and that's what it's all about right now."
White Sox ace Chris Sale (6-1) labored, giving up three runs and eight hits through six-plus innings. The left-hander allowed 11 baserunners and at least one in all but one inning, but he walked only one and struck out seven.
"I was good, but my fastball command was a little shaky," Sale said. "I really had to battle through it."
"Obviously, you know you've got your hands full with Hudson on the other side over there. He's been nothing short of dominant all year," he said.
Hudson (7-3) struggled in his shortest start of the year, permitting seven runs and 12 hits in 4 2/3 innings. He entered the game with an MLB-leading 1.81 ERA.
"You score six runs on a day I pitch, we should win these games," Hudson said "For me, that's the frustrating part."
"Giving up seven runs with a pitcher like they put out there in Sale, that's a tough hole to put those guys in."
Ronald Belisario pitched the final 1 2/3 innings to earn his seventh save.
San Francisco has allowed 35 runs in its last five games, and 53 in losing eight of its last nine.
"You get the hitting, the pitchers, they have their moments," manager Bruce Bochy said "That's what really puts you in a losing streak, but the only way you get out of it, hey, you focus forward and keep going hard."
Tyler Flowers singled up the middle with the bases loaded in the fourth to drive in two runs and extend Chicago's lead to 4-0.
The Giants cut it to 4-2 in the fifth when Buster Posey singled in a run and Pablo Sandoval hit a sacrifice fly. Dunn's homer to right against Hudson with none out in the bottom of the inning put Chicago up 7-2.
Sale was replaced by Jake Petricka with none out in the seventh after Juan Perez singled and Gregor Blanco walked. The Giants loaded the bases, but got only one run, on Posey's sacrifice fly to make it 7-3.
Blanco doubled in a run and Hunter Pence drove in another with a grounder off Zach Putnam. The Giants added their final run in the ninth on Tyler Colvin's sacrifice fly.
Dunn's homer was his 452nd, tying him for 35th with Carl Yastrzemski. ... Sale made his first career start against San Francisco. He hit two batters in the game after hitting only one all season. ... The game started 12 minutes late because of rain. ... Giants OF Angel Pagan (lower back) was out of the lineup for a third straight game and is listed as day-to-day. ... Posey was back behind the plate. He was at DH on Tuesday night after taking a foul off mask on Sunday. ... The White Sox open an 11-game road trip on Thursday night at Minnesota. Chicago's Jose Quintana (3-7) is scheduled to face Minnesota's Yohan Pino, who will make his MLB debut. ... The Giants' next game is at Arizona on Friday. Tim Lincecum (5-4) will face Josh Collmenter (4-4).
Abreu Homers in White Sox Win
Jose Abreu hit his 20th home run of the season as the White Sox handed the Giants their fifth straight loss, winning 7-6.