Porcello, whose questionable headfirst dive into first base recorded the game's first out, was booed off the mound after giving up six runs as the Chicago White Sox rolled to their seventh straight win, 9-2 over the Red Sox.
It was Boston's 12th loss in 14 games.
The Red Sox, who entered the night with a one-game cushion for the worst record in the AL, have been outscored 11-0 collectively in the first inning of the first three games of the series.
"We've been slapped in the face right from the get-go," Red Sox manager John Farrell said. "Three consecutive nights we find ourselves down multiple runs early in the ball game. Bottom line is we've got to do a better job of pitching, and that's not focusing on the starters — that's focusing on everyone."
Adam Eaton hit a leadoff home run on Porcello's fifth pitch and the struggling right-hander gave up a solo homer to Alexei Ramirez before getting the hook three batters into the third.
Porcello (5-11) hit a batter with the bases loaded and allowed seven hits and a walk in two-plus innings.
"Had a bad game," Porcello said. "Elevated some pitches, fell behind some guys, a couple walks with some runners on base. Put them in some tough spots and didn't recover."
Mike Napoli homered and drove in two runs for the Red Sox, who have dropped the first three games of the series and 11 of 13 since the All-Star break.
For the third straight game, the White Sox scored in the first inning, grabbing a 2-0 lead. Eaton hit his homer down the right-field line and Melky Cabrera scored when second baseman Brock Holt missed a relay throw from the outfield — with the ball going under his glove and rolling behind him for an error.
They added three runs in the second. Eaton and Cabrera had RBI singles before Porcello hit Adam LaRoche with a pitch with the bases loaded, making it 5-0.
Chicago chased Porcello by opening the third with three consecutive hits. Ramirez homered into the first row of Monster seats, Carlos Sanchez doubled and Tyler Flowers singled. Craig Breslow relieved and left the bases loaded.
Eaton and Cabrera both had three hits, including RBI singles.
Jose Quintana (6-9) allowed two runs and six hits, striking out three and walking one. He gave up Napoli's homer into the Green Monster seats in the seventh.
White Sox: INF Emilio Bonifacio (strained left oblique) was placed on the 15-day DL. He was hurt grounding out on Tuesday and had to be helped to the dugout.
Red Sox: CF Mookie Betts was placed on the seven-day DL with a concussion after tumbling backward over the bullpen wall Tuesday when he made a catch on the field but had the ball fall out of his glove for an overturned, replay-reviewed homer when he landed. ... 3B Pablo Sandoval left the game because he was dehydrated.
VIVA DOMINICANA NIGHT
A night after retiring newly inducted Hall of Famer Pedro Martinez's uniform number 45, the Red Sox held a ceremony retiring it again in Spanish. Fans were given Dominican flags and postcard replicas of his Hall of Fame plaque with the words in Spanish. The Red Sox played congratulatory messages from Dominican players around the majors, including Albert Pujols of the Los Angeles Angels.
White Sox: LHP Chris Sale (9-5) is slated to start on Thursday. He's 7-4 on the road with a 2.05 ERA.
Red Sox: Knuckleballer Steven Wright (3-4), who has been shuttled between Triple-A and the majors, is scheduled to make his seventh start. He did warm up early in Wednesday night's game.