Lysacek, 23, turned in a near flawless free skate program Thursday and moved from second after the short program to first. He totaled 242.23 points, just ahead of Canadian Patrick Chan, who had 237.58 points.
French skater Brian Joubert, who led after the short program, was third with 235.97 points. Joubert suffered an embarrassing face-first fall near the end of his program Thursday.
Lysacek took the gold with a program that included eight triple jumps. The Los Angeles Times said he was given positive grades of execution in 12 of 13 elements while Lysacek's spins earned the highest level by judges.
Lysacek is the first U.S. male to take the World Championships gold since Todd Eldredge in 1996.
In ice dancing, Russians Maxim Shabalin and Oksana Domnina own the lead heading into Friday's free dance, after which medals are to be awarded. Americans Tanith Belbin and Ban Agosto are second, less than 1 point behind the Russian duo.