Strasburg was in control until he got hurt, striking out six in 4 1/3 innings while allowing two runs and a run.
Craig Stammen relieved Strasburg with the Nationals leading the Phillies 5-1. Doug Slaten (3-1) pitched 1 2/3 shutout innings for the win.
Roger Bernadina hit a three-run homer, Ian Desmond had four hits and Ivan Rodriguez and Adam Kennedy each had two RBIs.
For the last-place Nationals, the win was overshadowed by the sight of Strasburg leaving the mound.
Manager Jim Riggleman immediately left the dugout to check on his ace almost as soon as the ball landed in catcher Ivan Rodriguez's mitt.
The Nationals will surely be cautious with Strasburg. The No. 1 overall pick in the 2009 draft, he was scratched minutes before his scheduled start against Atlanta on July 28 and was diagnosed with inflammation in his right shoulder. He was placed on the 15-day disabled list the next day.
When healthy, Strasburg has been as good as advertised. He's 5-3 with a 2.91 ERA and has allowed two or fewer earned runs in nine of 12 starts. He was throwing in the high 90s mph all night and had shut down the two-time defending NL champs.
Strasburg's first pitch of the game was a 97 mph fastball to Jimmy Rollins. Four pitches later, Strasburg struck out the former NL MVP looking on a buckling 83 mph curve.
Phillies manager Charlie Manuel said before the game he couldn't wait to get his first live look at the super-hyped prospect.
Strasburg was staked to a 3-0 lead before he threw a pitch. Phillies starter Kyle Kendrick (8-6) was hit hard all night. He walked Kennedy with the bases loaded, and allowed a two-RBI single to Rodriguez that made it 3-0.
Kennedy added an RBI single in the third and Strasburg hustled down the line on a force play to beat Rollins' throw, avoid a double play and drive in a run for a 5-0 lead.
Kendrick's erratic season as the No. 5 starter continued with a nine-hit, five-run outing over 5 2/3 shaky innings. He was loudly booed several times by the Phillies fans.
Phillies first baseman Ryan Howard singled off Strasburg in his first at-bat following a three-week layoff with a sprained left ankle. Howard's RBI groundout in the fourth was the only run scored against Strasburg.
Howard was robbed of an extra-base hit in the ninth on a way-up-there against the wall catch by Bernadina in left. Bernadina jumped as if he was trying to dunk a basketball -- and snagged the ball.
Bernadina's eighth homer was a liner to right off Chad Durbin in the ninth.
NOTES: Howard was hurt Aug. 1 sliding back into second base at Washington and was activated before the game. Howard played one rehab game on Friday night. He's batting .292 with 23 homers and 81 RBIs. To make room for Howard, outfielder Ross Gload was placed on the DL. Gload strained his groin on Aug. 11 against the Dodgers after hitting a double in the sixth inning.