Demba Ba opened the scoring with his eighth goal of the season after 28 minutes before Boubacar Sanogo marked his debut with a second on 63 after joining on loan from Werder Bremen earlier this month.
Hoffenheim, without top scorer Vedad Ibisevic who is out for the rest of the season with a ruptured cruciate ligament, put in another solid performance as they resumed their title chase in their first top-flight season.
"We are satisfied with the result but also with the way the team played for most of the game," Hoffenheim coach Ralf Rangnick told reporters. "They deserve a big fat compliment."
The Berliners, who this week renewed coach Lucien Favre's contract for another year, also missed a penalty when Cicero's effort was blocked by goalkeeper Markus Proell on 33 minutes.
Frankfurt pulled one back through Benjamin Koehler three minutes after Pantelic's second but failed to grab an equaliser despite putting Hertha under mounting pressure.
"We are very relieved with this result," Favre said. "Frankfurt put us under a lot of pressure at 2-0 but we hung in there. I had the intuition to play Pantelic."
The hosts led through a header from Switzerland's Alexander Frei's nine minutes before the break before Leverkusen's Patrick Helmes and Stefan Kiessling went close to levelling early in the second half but were denied by goalkeeper and cross bar.
Schalke 04's erratic season continued when hosts Hanover scored against
