He has a career .285 average from the spot, but was forced out of the familiar territory with his recent struggles at the plate.
Before Monday, Upton was hitless in his previous 10 at-bats in the Chicago series and was hitting .186 with eight hits and three RBIs in his previous 11 games.
Looking for offensive answers, D-backs manager Kirk Gibson moved Upton to the five hole, a spot he's only occupied 44 times in his career.
"It was inevitable the way I was hitting," Upton said. "I think it's a good move for the lineup for the time being and hopefully I'm back in the three hole at some point."
Despite Upton's hopes, the fifth spot may be a better fit for the six-year veteran.
Upton tallied three singles from the five-hole Monday with a walk, an RBI and a stolen base, and his .370 on-base percentage is the highest of any spot in the order where he's made more than 20 plate appearances.
"We had pretty good results [Monday] night," Gibson said. "We need offense right now. We try and get something productive out of everything we do. [Upton] has done everything I've asked, to be honest with you."
The recent moves are much-needed for Upton, who has faced some difficult times recently off the diamond as well.
Gibson said between the struggles at the plate, the constant trade talks and the criticism from the fans, this current stretch may be the toughest period of Upton's career.
"The thing he went through at home, people bullying him and stuff, that's all part of it," Gibson said. "He knows that everybody is counting on him. He knows it. That's a responsibility that is on him whether he likes it or not. He accepts it and he's attacked it the best he can. He doesn't give in by any means at all.
"It eats him up. It eats every guy in there."
But Upton has taken it all in stride.
While the two-time All Star said he prefers hitting third, he's willing to do whatever helps the team.
"It worked for us [Monday]," Upton said. "Hopefully it's something that kick-starts the team and gets us going."