The Fenerbahce striker netted the opener in Kufstein, Austria early in the second half as Cameroon began their final preparations for the World Cup, which starts next month, in winning fashion.
However, Webo appeared to injure his left shoulder while giving Cameroon the lead, leading to doubts over his participation in Brazil.
Cameroon's squad is due to be cut from 28 men to 23 by June 2 and, depending on the severity of the injury, Webo could now find himself on the outside looking in.
The blow to Webo will concern Cameroon boss Volker Finke, but the German will have been pleased with his side's clinical nature in front of goal, which was showcased again late on when Eric Maxim Choupo-Moting made sure of victory.
Cameroon had the better of an opening half that produced few chances.
Midfielder Landry N'Guemo had the game's first real opportunity as his drive at the near post was well saved by Macedonia goalkeeper Tomislav Pacovski.
Macedonia were forced into a change in the 26th minute as left-back Goran Popov was replaced by Ardian Cuculi after suffering a injury.
Finke's men continued to dictate play and could have taken the lead on the half-hour mark had Webo not headed over the bar when presented with a great opening from six yards out.
The African nation made one change at the break as keeper Guy Roland N'dy Assembe came on for Sammy Ndjock.
Cameroon then broke the deadlock as Webo found the net in the 52nd minute with an acrobatic close-range bicycle kick after Fabrice Olinga's effort had deflected into his path.
However, the forward landed awkwardly on his shoulder in the act of scoring and was immediately substituted, with Mohammadou Idrissou coming on in his stead.
Cameroon were then thankful to N'dy Assembe for keeping them in the lead as he pulled off a brilliant save prior to Choupo-Moting's fine goal in the 84th minute.
The Mainz forward turned the ball into the bottom corner with a well-placed half-volley, before seeing an injury-time strike disallowed for offside as Cameroon earned a morale-boosting win ahead of further pre-tournament friendlies with Paraguay, Germany and Moldova.
