Left-hander Francisco Liriano held the Reds to one run on four hits over seven innings and was backed by two home runs from catcher Russell Martin as a standing-room only crowd of more than 40,000 waved black hankies and roared their support at Pittsburgh's first playoff game in 21 years.
The victory advanced the Pirates to the best-of-five Division Series against the top-seeded NL Central champion Cardinals starting on Thursday in St. Louis.
Second-inning home runs by Marlon Byrd and Martin off Reds' starter Johnny Cueto got the Pirates started and they added another run in the third on a sacrifice fly by Pedro Alvarez for a 3-0 lead.
Cincinnati got on the scoreboard with a fourth-inning run that made it 3-1 when Jay Bruce's two-out single to left scored Choo Shin-Soo, who became the first Reds player to reach base when he was hit by a pitch leading off the frame.
But the Pirates extended the lead in their half of the fourth with two more runs after doubles by Starling Marte and Neil Walker that made it 5-1, and Martin crushed another home run off reliever Logan Ondrusek in the seventh.
Choo got the Reds one run closer with a home run in the eighth but it was not enough as Pittsburgh won in the postseason for the first time since 1992.