Last year's National League Rookie of the Year batted second in the lineup and played three innings in left field before being pulled.
Harper hadn't played since May 26 and was put on the disabled list June 2 with bursitis in his left knee. Entering Monday, Harper had missed 25 straight games and 31 of the first 75 this season for Washington.
"He looks the same-old Harp," said Potomac manager Brian Daubach who also had Harper in Hagerstown in 2011.
After having the best record in the majors last season at 98-64, the Nationals have struggled without Harper and are 37-38.
Harper wore a knee brace during warm-ups, but it wasn't visible during the game.
In Harper's first at-bat he hit a pop-up into shallow left field that was dropped by Myrtle Beach shortstop Edwin Garcia. Harper showed no signs of the knee ailment as he raced around first base and into second for a stand-up double.
"The double he hit was a blooper down the left-field line and he was flying," said Daubach. "It's as good as I've seen him run."
Moments later, Harper was picked off by Pelicans pitcher Blake Schwartz after taking a large lead and failing to slide back in time to beat the throw.
"He's aggressive," Daubach said. "When he got second, looking to take third in a situation with one out, all positive for me."
In the third inning, Harper got a late start on Rougned Odor's shot into left field. The left fielder recovered to make up ground but the ball bounced over the wall for a ground-rule double.
Harper's second at-bat ended after seven pitches with a walk.
"I know he's been out awhile, and as you see with most rehab guys, the more at-bats they get they get it back," Daubach said. " But to have the second at-bat be a long at bat and to lay off some good pitches was a good sign."
The next batter, Jason Martinson, doubled Harper to third. Again Harper's knee looked fine as he raced around the bases so fast that his helmet couldn't keep up and flew off his head before reaching third.
Harper wasn't at third base long as the next hitter, Adrian Nieto, singled him home. Harper, still the youngest player on the team, picked up Nieto's bat before crouching down and cheering as Martinson slid home to even the game 3-3.
Potomac defeated Myrtle Beach 7-5.
Although admitting to not having the final say, Daubach answered that Harper playing six innings on Wednesday "sounds about right."
"After playing for the first time in a while, hopefully he comes back ready to go tomorrow," said Daubach.
Harper's appearance with Potomac could be felt early on as long lines were visible outside the stadium as early as two hours before the first pitch. Harper's batting practice also caused quite a scene as more than 100 fans crowded around the cage, while others looked on from the top row of the first-base stands. Many in attendance wore Harper's jersey, while others took pictures trying to get a glimpse of the all-star.
Kids chanted his name from atop their father's necks and teenage girls gave him the rock star treatment by screaming as he was led by police officers back to the dugout after the session.
It was the first sellout of the season for the Potomac Nationals.
"On a Tuesday night it can get slow around here," Daubach said. "It wasn't the normal Tuesday night for us for sure."
Manager Davey Johnson, speaking before Washington's game against Arizona, said Harper likely won't rejoin the Nationals this weekend when they travel to New York.
"I doubt if he'll be able to make it that quick," Johnson said, pointing to a series starting next Monday in Washington against Milwaukee for Harper's likely return. "He'll probably do three or four innings tonight, and then, if there's no problem, gradually up it."