PHILADELPHIA _ Javier Baez was scratched from Thursday night's lineup because of a high fever, and the Cubs missed the All-Star shortstop's defense at a critical time.
David Bote, making his second major league start at shortstop, committed a fielding error with one out in the bottom of the ninth with a four-run lead.
The Cubs' bullpen continued the slide as Rowan Wick and Pedro Strop allowed three hits and a hit batsman.
That set up Bryce Harper's towering walk-off grand slam off Derek Holland to hand the Cubs a 7-5 loss to complete a three-game sweep and ruin a dominating performance from Yu Darvish.
The Cubs remained percentage points behind the Cardinals in the National League Central. More disturbing for the Cubs is their penchant for finding ways to lose on the road. They lost for the 16th time in their last 24 games.
Until the ninth, the Cubs cruised behind Darvish, who struck out 10 in seven innings.
Anthony Rizzo christened his return to the leadoff spot with a home run and Kyle Schwarber hit the 100th home run of his career.
This marked the second time this season that Darvish struck out at least 10 and walked none.
Darvish has struck out 63 while walking only two, lowering his ERA from 4.98 to 4.21, in his last eight starts.
Darvish hasn't walked a batter since July 23 and became the first Cubs pitcher since 1908 to strike out at least eight batters and walk none in in four consecutive starts.
Darvish held the Phillies to no hits in nine at-bats with runners in scoring position.
Meanwhile, Rizzo sparked an offense that scored only three runs in its two previous games against the Phillies. Rizzo smacked a towering shot off left-hander Drew Smyly that barely reached the seats in right center to give the Cubs a 1-0 lead in the third.
The homer was Rizzo's first since July 27 at Milwaukee. It was only his second extra base hit in August, but it seemed to spark the rest of the lineup.
In the fourth, Ian Happ waited patiently before poking an off-speed pitch by Smyly off the right field fence for a triple. He later scored on a double by Bote.
Albert Almora Jr., who entered the game batting .210 against left-handers, hit a two-out single into right to score Bote. Rizzo capped the rally with an RBI single to right.
Schwarber set a franchise record by becoming the fastest to reach 100 home runs in his 453rd game with the Cubs, according to historian Ed Hartig.
Schwarber's homer off Smyly with one out in the fifth landed in the shrubs to the right of the 409-foot sign in center field.
