The Croat, aged 37 and five months, beat Luxembourg's Gilles Muller 6-7 (2-7) 7-6 (7-5) 7-6 (14-12) to claim his seventh career title.
Marty Riessen won in Lafayette in 1979, aged 37 years and nine months.
At the French Open this year Karlovic became the oldest man for 25 years to reach the third round of a Grand Slam.
Ivo Karlovic became the oldest ATP Tour title winner for 37 years with victory in the Hall of Fame Championships in Newport, Rhode Island.