Oxford made five changes to the team that went down 2-0 at home to Southend, and the youngsters brought in helped them to turn in an improved performance.
James Constable saw a powerful shot on the turn parried by Trevor Carson, who also saved a header from the striker in the second half.
But Pompey grew in stature as the clash at the Kassam Stadium went on. Sonny Bradley shot straight at Clarke, and John Marquis volleyed over from distance.
Agyemang had only been on the pitch for five minutes when he struck a brilliant 65th-minute shot with the outside of his right foot from the edge of the area to beat Ryan Clarke.
Clarke pulled off fine stops from Agyemang and Marquis but he was beaten again the 82nd minute, Marquis headed in Yassin Moutaouakil's right-wing cross.
Constable pulled a goal back from close range with a minute left but it was too late as Guy Whittingham's team avenged their 4-1 thumping by Oxford at Fratton Park on the opening day of the season.