Infielder Jedd Gyorko (50), pitcher Max Fried (53), outfielder Rymer Liriano (55), pitcher Casey Kelly (69) and catcher Austin Hedges (73) all made the list.
It's the second time Gyorko, Kelly and Liriano made the Top 100 list, as those three were among the six players from the organization on the 2012 list.
The annual ranking of baseball's biggest and brightest young talent is assembled by MLB.com's Draft and prospect expert Jonathan Mayo, who compiles input from industry sources, including scouts and scouting directors. The rankings are based on an analysis of players' skill sets, upsides, closeness to the Major and potential immediate impact to their respective teams. The list, which is one of several prospect rankings on MLB.com's Prospect Watch, only includes players with rookie status in 2013.
Gyorko figures to make his Major League debut this spring, as he'll get a crack at winning the second-base job during Spring Training.
Gyorko hit .328/.380/.588 last season with Triple-A Tucson, hitting 24 home runs to go with 83 RBIs, all after beginning the season with Double-A San Antonio, where he hit .262 in 34 games. He's regarded as the top second-base prospect in the Minor Leagues, according to MLB.com.
Fried, the seventh overall Draft pick last June, will likely begin his first full professional season this spring with Class A Fort Wayne. Fried, a left-hander, got his first taste of professional baseball last summer, as he went 0-1 with a 3.57 ERA in 17 2/3 innings with the Padres' short-season team in Arizona.
Fried was recently named the third-best left-handed pitching prospect in the Minor Leagues by MLB.com.
Liriano had a .280/.350/.417 slash line in 2012 with Class A Lake Elsinore and San Antonio. He hit eight home runs, had 32 doubles and knocked in 61 runs to go with 32 steals. He then kept impressing during the Arizona Fall League, hitting .319 with four home runs in 22 games.
"He had a little slow start in Cal league and then played exceptionally well," said Randy Smith, the Padres' vice president of player development and international scouting. "The learning curve is becoming shorter for him. He's hitting the ball to all fields with authority."
Kelly made his Major League debut with the Padres last season, going 2-3 with a 6.21 ERA in eight starts. He missed three months of the season with a strained right elbow ligament after beginning the season with Tucson. Kelly will be in the running for a spot in the Padres' starting rotation this spring.
Hedges completed his first full season of professional baseball in 2012. Regarded as a strong defensive catcher, Hedges impressed with his bat as well in helping Fort Wayne reach the postseason. Hedges hit .279 with 10 home runs and 56 RBIs. He had 14 stolen bases as well.
Hedges, who will begin the season with Lake Elsinore, figures to gain valuable experience this spring, as he's been invited to big league camp. He was recently rated as the fourth-best catching prospect in the Minor Leagues by MLB.com.
"He knows what he's trying to do with each pitch, each at-bat, and he stays in the middle of the field," Smith said. "Behind the plate, he's cleaned up a lot of things in the last half of the year. I think it's just the progression of catching every day, knowing you can't take a pitch off."