The Nationals will showcase the rest of their rotation in a home series that starts Monday, with their next win clinching the franchise's first winning season since 2003.
Strasburg pitched six scoreless innings for Washington (81-52) in Sunday's 4-3 win over St. Louis. His effort helped the Nationals lower their starters' ERA to 3.28, the best mark in baseball.
"We're going to see the best team in baseball the next four days," manager Dale Sveum told the Cubs' official website. "Even though we miss Strasburg, we're still going to see four quality starters and a heck of a lineup that they can throw at you."
Washington owns baseball's second-best record and will also likely have two members of its lineup back after Jayson Werth and Adam LaRoche did not start Sunday.
Werth was held out after leaving Saturday's loss to the Cardinals with leg cramps. LaRoche, who flied out as a pinch-hitter, did not start due to a sore back.
"I'll probably have to wrestle them to keep them out of the lineup (Monday)," manager Davey Johnson told the Nationals' official website.
The Washington franchise last posted a winning record when the Montreal Expos won 83 games nine years ago. The Nationals have won 11 of 15 at home.
Ross Detwiler (8-6, 3.32 ERA) will start the opener for the Nationals. He's 3-1 with a 1.67 ERA in five home starts since the All-Star break.
Detwiler yielded three runs over 5 2-3 innings Wednesday to earn an 8-4 victory at Miami. He went 1-1 with a 4.35 ERA in his two career starts against the Cubs last year.
Chicago (51-82) is starting a 10-game trip and has lost 13 of 14 on the road.
The Cubs fell to 4-6 halfway through a stretch in which they play 20 straight days with Sunday's 7-5 defeat to San Francisco.
Sveum says that he wants to give regulars Alfonso Soriano, Starlin Castro and Anthony Rizzo some rest, but not necessarily when facing a contender.
"You have to pick those days and figure out who needs them mentally or physically," the manager said. "It's a little bit of a crap shoot sometimes."
Washington took two of three in Chicago to open the season. The Cubs avoided the sweep when Jeff Samardzija (8-12, 4.03) pitched them to a 4-3 victory in the finale April 8 as he struck out eight and came within an out of a complete game in his lone career start against the Nationals.
Samardzija has pitched at least seven innings in four of his last five starts entering this one. He lasted that many frames and gave up three runs Wednesday in a 3-1 home loss to Milwaukee.
He'll get his first look at Bryce Harper, who wasn't with Washington on opening day. Harper went 0 for 4 on Sunday after the rookie All-Star posted four straight multihit efforts for the first time, homering three times with eight RBIs during that surge.