Gojowczyk fired 12 aces of his own and saved one break point in each set of his 7-6 (7/5), 6-7 (1/7), 7-6 (7/4) triumph over two hours and 26 minutes at the Newport, Rhode Island, grasscourt event yesterday.
The 28-year-old from Munich booked a Saturday semi-final date against 249th-ranked Australian qualifier Matthew Ebden, who rallied to oust Germany's Tobias Kamke 4-6, 7-6 (8/6), 6- 4.
Each semi-finalist seeks his first ATP singles title.
Karlovic pulled level at 4-4 in the tiebreaker but dropped the next point on his serve and the German took the final two points on his serve to dethrone the champion, who finally won last year after 2014 and 2015 Newport finals defeats.
Karlovic also lost his only prior match with Gojowczyk at Beijing in 2014.
Ebden, who won his only prior match against Kamke in the first round of the 2014 US Open, needed two hours and 41 minutes to subdue his 185th-ranked rival at Newport.
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