The blast carried an estimated 477-feet for the fifth-longest home run of the season, according to Statcast. Reyes' solo shot had an exit velocity of 111 mph.
San Diego earned its first lead of the game on Hunter Renfroe's sacrifice fly in the top of the first inning. Freddy Galvis gave the Padres a 2-0 advantage with a solo home run in the top of the second inning off of Cubs starter Jon Lester.
Eric Hosmer also had an RBI triple in the second frame, scoring Jose Pirela and Joey Lucchesi.
The Cubs finally got on the board in the third inning on Javier Baez's 24th home run of the season. Reyes stepped up to the plate in the bottom of the fourth inning for some insurance.
The Padres right fielder went up 3-0 in the count before Lester tossed a 90.1 mph fastball into the zone. Reyes swung his bat hard, raking the offering onto a roof beyond the center field fence for another solo home run. Reyes had a launch angle of 24 degrees on the blast. The home run was the longest hit this season at Wrigley Field.
Chicago scored twice in the fifth inning, closing the gap to 5-3. The Cubs tied the game at 5-5 in the bottom of the seventh inning. Corey Spangenberg earned the lead back for the Padres with an RBI double in the eighth frame, before Hunter Renfroe smashed a two-run homer in the top of the ninth inning for an 8-5 edge.
Travis Jankowski plated two more runs on an RBI single in the ninth inning, giving the Padres a five-run lead.
Ben Zobrist hit the final home run of the evening, smacking a solo shot off of Padres reliever Kirby Yates in the bottom of the ninth inning, but the Cubs could not complete a comeback.
The Cubs and Padres tied the four-game series 2-2. Chicago battles the Kansas City Royals in a three-game series, starting Monday at Kauffman Stadium in Kansas City. The Padres play the Milwaukee Brewers in a three-game face-off, starting Tuesday at Miller Park in Milwaukee.