Votto drove a 3-0 pitch from Boone Logan (1-1) over the wall in center for his fifth homer. Votto's fourth career game-ending shot traveled an estimated 437 feet.
"The older you get and the longer you play, the more I become one with the team," he said. "All you care about is winning."
Votto had been struggling coming into the game, and the Reds were coming off consecutive 4-3 losses in Boston. The Red Sox won in 12 innings on Tuesday, and then scored two in the eighth inning of Wednesday's victory.
"At the end of the year, you'll look up and I'll be about the same," Votto said. "The frustrating part is my struggles have coincided with a number of close losses."
Reds manager Bryan Price switched Votto from second in the batting order to fourth to try to give him more chances to hit with runners in scoring position. That didn't work out but Votto was came up at the right time for the Reds.
"It is really fun to watch guys have moments like that," Price said. "It was a big win for all of us. In a tie game, he has the green light."
Arenado went 0 for 3, snapping his hitting streak at a club-record 28 games, the longest in the majors this season. But he also walked and scored on Justin Morneau's tying double in the ninth, handing Jonathan Broxton (1-0) his first blown save in six opportunities.
Johnny Cueto had another strong outing for Cincinnati, striking out eight in eight innings of two-run ball. The right-hander allowed five hits and walked one.
"We knew it was going to be tough to score runs on Cueto," Rockies manager Walt Weiss said. "He's been locked in. We knew we had to scratch and claw. We battled every at-bat and made him earn every out."
Cueto has pitched eight or more innings in five consecutive starts. He has gone at least seven in each of his eight starts this season.
"I continue to move the ball in and out, like Bryan Price wants me to do," Cueto said. "I am thankful that I feel well and able to do my job. They have a good team. They made me work."
Colorado's Jhoulys Chacin, making his second start of the season after missing the first month with a right shoulder strain, allowed two runs and four hits in six innings.
Todd Frazier drove Chacin's first pitch of the second inning 485 feet to a party area above the center-field batter's eye. Frazier's sixth homer of the season was the sixth-longest in the 12-year history of Great American Ball Park.
Troy Tulowitzki led off Colorado's fourth with his 10th homer, a 404-foot shot on Cueto's first pitch that bounced off the roof over the Reds' bullpen bench in left-center field.
Pinch-hitter Billy Hamilton greeted Logan with an opposite-field double down the right-field line in the eighth inning. Schumaker sacrificed Hamilton to third base, setting up Pena's sacrifice fly.
Frazier extended his hitting streak to nine games, matching his career high. ... Weiss was pleasantly surprised that Morneau missed just one game with neck stiffness. Morneau, who has a history of neck problems, was scratched from Thursday's game at Texas, but started Friday at Cincinnati. "I didn't think it would be too long, but I thought it would be a couple of days," Weiss said. ... The Reds will most likely activate LHP Aroldis Chapman from the disabled list on Saturday, manager Bryan Price said. The team wanted to give the closer an extra day after he pitched on consecutive days for the first time on Tuesday and Wednesday to wrap up his rehab assignment. Chapman was struck in the left eye and nose by a line drive during a spring training game on March 19.