Continuing from where they left off last season, Hoffenheim were dangerous in the first half, and Adam Hlozek came close with a half-volley from the edge of the box that flew just wide.
Die Kraichgauer did find the breakthrough before the half-hour mark, with Bambase Conte feeding debutant Adam Daghim just outside the area, where he struck well inside the near post.
Yet Cologne should have equalised before half-time through talisman Said El Mala, who could not add to his 13 league goals from the previous campaign as his close-range effort was smothered by Oliver Baumann.
Considering that Hoffenheim dropped the fewest points from winning positions of any side in the Bundesliga last term (six), Koln had it all to do in the second half.
However, they came out flying and were quickly level, with the ever-involved El Mala cutting inside and finding the bottom corner via a deflection.
The hosts were looking confident, and El Mala was sent on another mazy run, which resulted in Paul Okon-Engstler firing narrowly over.
But with the hosts a little too eager to take the lead, Hoffenheim caught them on the break, prompting Jahmai Simpson-Pusey to naively bring down Conte in the box for a penalty. With regular taker Andrej Kramaric on the bench after injury, substitute Max Moerstedt stepped up after scoring against Erzgebirge Aue in the DFB Pokal, but Marvin Schwabe dived the same way to keep it out.
Approaching an hour on the clock, Moerstedt saw another golden chance saved by Schwabe, who closed him down well on the angle.
Koln were equally as threatening down the other end though, and El Mala was denied by Baumann as his shot looked to be curling into the far corner again. From the resulting corner, Luka Lochoshvili glanced his header inches wide.
Yet in Hoffenheim’s next attack, they retook the lead via a corner of their own. Vladimir Coufal whipped in a dangerous ball, and it was no surprise when Ozan Kabak met it with a bullet header after scoring in this fixture last season.
Undeterred, two Koln substitutes combined to bring them level again when Linton Maina crossed for Thijs Dallinga to sweep home on his Bundesliga debut.
Amazingly, he then bagged his second and the winner after the ball broke to him in the box, where he showed his predatory instincts to rifle home.
As a result, Koln record their fourth opening-day win from their last five in the Bundesliga (L1), while Hoffenheim miss the chance to set what would have been a new club record of three successive opening-day top-flight victories.