Loaiza gave up the three runs on a two-run double by Ryan Klesko, scoring Gary Matthews Jr and Mark Kotsay, and a RBI-triple by Mark Loretta in the third inning.
Down 2-0, Magglio Ordonez homered and Paul Konerko singled in Carlos Lee to tie the game at 2-2 in the second inning. Lee singled, stole second and advanced to third on a throwing error by catcher Gary Bennett in the inning.
The RBI for Konerko was the first of two for him in the game and his first RBI since May 21. Konerko tied the game again in the fourth, driving in Lee on a sacrifice fly.
Padres starter Kevin Jarvis pitched five innning, giving up three runs. The last two runs came off reliever Scott Linebrink.
Rios' homer, his second of the season, put the Sox up 4-3. Frank Thomas put the final run on the board with a solo home run of his own in the eighth.
Tom Gordon relieved Loaiza, who struck out four, and threw 1 2/3 scoreless innings to pick up the win. Damaso Marte threw 1 1/3 scoreless innings and Billy Koch threw a 1-2-3 ninth, earning his seventh save.
Game two of the series will be played on Saturday at 6:05 p.m. CT and will be televised on WGN. Danny Wright is scheduled to start against fellow righty Brian Lawrence.
NOTE: Brian Tollberg, who was originally scheduled to start the final game of the series, was demoted on Friday. Lefty Oliver Perez will start in his place on Sunday.