Moyer, who was 49 plus 141 days, surpassed the record set in 1932 by Jack Quinn of the Brooklyn Dodgers, who was 49 years and 70 days.
Moyer (1-2) compiled a solid line of six hits and two unearned runs over seven innings.
Dexter Fowler had a two-run homer for Colorado and Wilin Rosario drove in a pair of runs as well. Rafael Betancourt allowed a solo home run by Nick Hundley in the ninth but held on for his third save.
Chris Denorfia went 4-for-4 and scored a run for San Diego. Anthony Bass (0-2) took the loss, giving up three runs on four hits and three walks over five innings.