The O's face a stiff challenge in St. Louis, which has won four of five, including Thursday's 5-2 win over Boston.
Starter Adam Wainwright was solid in that victory, allowing just two runs while striking out seven to earn his 14th win of the season. Kolten Wong went deep twice to ignite the offense.
Meanwhile, no team in the majors has matched Baltimore's 22-10 record since the beginning of July, as the Orioles have extended their lead in the AL East to five games over the New York Yankees and Toronto Blue Jays.
The Orioles have not lost two in a row since June 28-29, and they have won four of their last five games following Thursday's 2-1 triumph in Toronto.
O's catcher Caleb Joseph has gone deep in four straight games.
Joseph homered in the seventh inning of Thursday's victory. He has driven in seven runs over his past four games and is hitting at a .342 clip (13-for-38) during the last 11 games.
Baltimore will send Chris Tillman to the mound for Friday's opener. The right- hander pitched seven shutout innings against Seattle his last time out, allowing just four hits while striking out six and walking nobody.
Tillman is 3-2 with a 2.45 ERA over his last 10 starts.
The Cardinals will send newly-acquired Justin Masterson to the mound. The right-hander has spent some time on the disabled list recently with right knee soreness and is still adjusting to his new digs in St. Louis after spending the last five seasons pitching for Cleveland.
In his first start for the Redbirds, Masterson gave up five runs in six innings against Milwaukee last week.
"I don't think you necessarily expect it, but you know some (rust) is going to be there," Masterson said. "I didn't think it would be perfect, but I thought it would be a lot better than before."
It marked the 10th time this season Masterson has allowed five runs in a start, and it was hit 11th time in the last 13 starts walking at least three batters.
The Cardinals have not faced the Orioles since sweeping a three-game set in Baltimore in 2011.