Seppi stunned Roger Federer in Melbourne by inflicting a third-round defeat on the 17-time grand slam winner, and was a whisker away from the quarter-finals but fell in five sets to Nick Kyrgios.
Seeded fifth this week in Croatia, the Italian began with a 6-2 3-6 6-4 win against Holland’s Robin Haase.
The tournament’s 2012 champion, Russian Mikhail Youzhny, slugged out a three-set victory over Blaz Kavcic to set up a second-round clash with Sergiy Stakhovsky of Ukraine.
Sixth seed Youzhny had a mid-match scare but held off Slovenian Kavcic, recording a 6-3 1-6 6-4 win.
Seventh seed Viktor Troicki fought back from a set down to see off qualifier Illya Marchenko. The 28-year-old Serbian, looking for his third career title and second of the year, claimed a 4-6 7-6 (7/3) 7-6 (7/3) victory over his Ukrainian opponent.
Marcos Baghdatis, who defeated Ivan Ljubicic to win the 2007 Zagreb title, trailed to Croatian wild-card entry Toni Androic but the world number 67 from Cyprus eventually claimed a 6-7 (3/7) 6-2 6-3 comeback success to set up a clash with top seed and home favourite Ivo Karlovic.
Damir Dzumhur of Bosnia saw off German Michael Berrer 6-2 0-6 7-5. Berrer’s two career finals have curiously come in Zagreb, but there will not be a third this year.
Japan’s Go Soeda fought hard to move past German qualifier Matthias Bachinger as he recorded a 7-6 (7/4) 7-5 triumph.