Upson tried his luck from 30 yards and the ball flew past goalkeeper Nikki Bull, who got a hand to it but could not prevent the goal.
Upson almost doubled the score on 38 minutes when his close-range effort beat Bull but Danny Foster scooped the ball off the line.
The Chairboys played some attractive attacking football but their finishing let them down as twice before half-time Joel Grant fired narrowly wide after promising moves and in the second half it was almost all Wycombe until the latter stages.
The best chance of an equaliser came on 75 minutes when Elliot Benyon thought he had scored with a close-range header but Yeovil's loanee keeper Jed Steer brought off a fantastic save.
As Yeovil went for the second goal that would have made sure of the points Gavin Massey, on loan from Watford and making his debut as a substitute, was inches wide of the far post after a fine run.