Simon, signed by Philadelphia in 1999 as an undrafted free agent, has faced Tampa Bay six times in 72 big-league outings but only once in a starting role. That came back in 2008 when, in his first start in the majors, he allowed three runs and struck out six over 7 2/3 innings in a 7-5 Rays win.
His five subsequent meetings have all been in relief, including a 4 2/3-inning stint on June 12 in Baltimore, where he allowed an earned run on five hits in a 9-6 Tampa Bay win.
Simon defeated Minnesota with eight innings of one-run ball on Aug. 23, but dropped a 3-2 decision to the Yankees in his last start on Aug. 29.
For the Rays, soon-to-be 26-year-old righty Wade Davis again looks for a first win since July 28.
Davis tossed six innings in a 10-8 triumph at Oakland to get to 8-7 on the season, but is 0-1 in five starts since, though the Rays have won four of those games.
He lasted just 4 1/3 innings and surrendered six runs in a 7-3 loss at Toronto on Aug. 29, one start after getting a no-decision in a 3-2 Tampa Bay win over Detroit, in which he went nine innings and allowed two runs.
The Rays won the game in the bottom of the 10th.
Davis is 5-3 in nine starts against Baltimore with a 3.72 earned run average in 58 innings.
Baltimore captured the opener on Friday night, when J.J. Hardy capped a three- run seventh inning with a two-run single en route to a 3-2 win.
Nolan Reimold also drove in a run in the seventh for the Orioles, who had lost four of five.
Baltimore starter Zach Britton (9-9) gave up two runs on four hits over six innings to pick up the win. He struck out six and walked three.
Evan Longoria knocked in two runs for the Rays, who have lost four of five.
David Price (12-12) allowed three runs on four hits over seven innings to take the loss. He struck out 11 and walked three.
The loss dropped the Rays nine games back in pursuit of the American League's Wild Card berth.
The Orioles have won seven of 13 over the Rays so far this year, taking six of seven at Tropicana Field.