Big-serving Croatian Karlovic delivered 17 aces on his way to a 7-6 (7-2) 6-2 win over American wildcard and 2003 champion Robby Ginepri on the grass courts at Newport.
Karlovic, the second seed, only faced one break point as his serve helped him into the second round.
The world number 31 only lost four points on serve in the first set and six in the second before completing his victory in an hour and four minutes.
Young was the only seed to fall on Monday, beaten by another big server in Australian Sam Groth 7-6 (9-7) 6-2.
Groth mixed 11 aces with six double faults and saved a set point against the fifth seed in the first-set tie-break.
He broke for 3-1 in the second and again when Young was serving to stay in the match.
Awaiting Groth in the second round is Tunisian Malek Jaziri, who overcame Lithuanian Ricardas Berankis 7-5 6-3.
American sixth seed Steve Johnson needed just 47 minutes to crush countryman and wildcard Clay Thompson 6-1 6-2.
Rajeev Ram, the American who won the ATP 250 title in 2009, claimed a 6-2 7-5 victory against Australian Matthew Ebden.
Elsewhere, Japan's Tatsuma Ito beat American wildcard Mitchell Krueger 7-6 (9-7) 6-1 and Israeli Dudi Sela was a 6-1 7-6 (7-2) winner against Poland's Michal Przysiezny.