The Portuguese striker got the home side off to a flying start in the fourth minute, holding off Aleksandar Dragovic's challenge after he was played through by Danny da Costa and staying cool to beat goalkeeper Lukas Hradecky.
Dragovic's evening went further downhill 12 minutes later, when he conceded a clear penalty for handball. The Austria defender was booked and Paciencia converted the spot kick for his second goal.
Leverkusen pushed hard for a way back, but found Frankfurt goalkeeper Frederik Rönnow in fine from.
Rönnow blocked Lucas Alario's effort and Julian Baumgartlinger's rebound attempt before Frankfurt launched a counterattack that ended with Paciencia using his heel to set up Bas Dost to score. The goal was ruled out, however, as the Dutch forward was just offside.
Leverkusen were awarded a penalty in the 71st when Gelson Fernandes appeared to handle the ball, but referee Christian Dingert changed his decision after consulting video replays. The ball struck Fernandes' face.
Dost finally sealed the result in the 80th minute after holding off three defenders to prod the ball past Hradecky.
Frankfurt joined Leverkusen and four other teams on 14 points, two behind early leader Borussia Mönchengladbach.