With Aussie tennis fans buoyed after Nick Kyrgios' Wimbledon exploits, Tomic needed two hours and 46 minutes to advance to the final, beating the Dominican Republic's Victor Estrella Burgos 7-6 (7-2) 6-7 (5-7) 7-6 (7-5).
The Australian wildcard delivered 21 aces as he reached his first decider since the Sydney International in January.
Rain saw the third set interrupted, much to the benefit of Tomic as the 21-year-old appeared to be suffering from cramp.
On resumption, Tomic fell behind 3-1 in the third-set tie-break before responding with four straight points.
Scores were locked at 5-5 before a powerful Tomic forehand gave him match point and he collapsed onto his back at the net after completing the hard-fought win.
Croatian second seed Karlovic served 22 aces in a 6-4 3-6 6-4 win over fellow veteran Radek Stepanek of the Czech Republic.
Stepanek had his chances but could only convert one of six break points in the semi-final at the ATP 250 event, which is played on hard courts in Bogota.
Karlovic's big serve dominated the deciding set as fourth seed Stepanek managed to win just three return points.
It looked headed for a tie-break before Karlovic broke to love in the 10th game to seal his win.
Karlovic became just the fourth player to reach four or more finals this year, joining elite trio Rafael Nadal, Novak Djokovic and Roger Federer.