The ball hit off the end of Upton's glove, carried over the fence, and Grandal trotted around the bases for what proved to be the game-changing hit in San Diego's 8-6 win at Chase Field.
The victory, the fifth in a row for the fourth-place Padres, completed the club's first three-game sweep of the D-backs at Chase Field.
"Our time here in my tenure and even prior to me, this has been a tough place to play," Padres manager Bud Black said. "I can't explain it. I know the Diamondbacks feel confident here as evident by their record over the years here."
The win also completed a 10-game road trip with an impressive 7-3 record. Overall, the Padres have won eight of their past 11 games and return to San Diego on a winning streak for four games against the Reds.
"It's good to see," Black said. "There is a continuity going on in all phases of the game. It starts with pitching and defense and when that happens, the offense senses opportunity and cashes in on them. We are swinging the bats much better."
Here's something else to think about: The Padres trail the third-place D-backs, losers of five in a row, by seven games in the win column and already are talking about making a push in the second half of the season.
Perhaps, but who could have predicted that four of Grandal's six hits this season would be home runs? Or that the first three hits of his big league career would be homers?
"If you would have told me I was going to hit four home runs in five games I would say, 'No way,'" Grandal said. "I am definitely surprising myself. It's unexplainable."
Padres starter Jason Marquis also did his part. The right-hander was charged with four runs on eight hits in 6 1/3 innings to keep his team within striking distance. He struck out seven and walked one batter.
"He cinched his belt and gave us five much-needed zeroes," Black said. "He got the ball down and his slider improved. He has it in him. He has that mentality. There is no quit in him."
Neither team quit Wednesday.
Tied 3-3 with two outs in the seventh inning, Padres right fielder Chris Denofria hit a single to right field and stole second base with Alexi Amarista at the plate. Amarista followed with a run-scoring single up the middle to push the Padres ahead, 4-3. The D-backs then tied the game with a run in the bottom half of the frame.
Trailing 3-1 in the top of the third inning, Padres first baseman Yonder Alonso drove home Amarista with a single to right field to cut into Arizona's lead. The next inning, Marquis hit a two-out RBI double that scored Everth Cabrera to tie the game.
A three-run home run by D-backs left fielder Jason Kubel gave the home team an early 3-1 advantage in the first inning but it was Grandal's blast that proved to be the hit -- and near-catch -- of the night.
"When I saw [Upton] jump, I knew it was out but I thought he was going to catch it," Grandal said. "Once I saw that ball drop, it was a relief. It happens. Maybe in another situation, he comes up with it. Today, it went my way, and another day, it goes their way."