Wolves went into the Premier League fixture against the Cottagers with Craig Dawson having joined Matheus Cunha and Hwang Hee-chan on the unavailable list.
During the first half at Molineux, things went from bad to worse for O'Neil as attacking duo Jean-Ricner Bellegarde and Pedro Neto each suffered injuries.
Bellegarde sustained a knee issue while just before half time, Neto was forced to be withdrawn with another hamstring injury, this time to the opposite leg that he suffered a similar problem with in October.
However, despite having just one senior attacking player on the pitch in Pablo Sarabia, with 19-year-old forward Nathan Fraser making his first start, Wolves were able to collect maximum points.
Rayan Ait-Nouri's opener was followed by a Nelson Semedo strike that was deflected into his own net by Tom Cairney, Fulham's consolation coming from Alex Iwobi in the eighth minute of added-on time.
Despite quickly being left with a depleted attacking contingent and losing their clean sheet in the final seconds, O'Neil described the success as his "favourite" during his reign.
O'Neil said, as quoted by the Express & Star: "It's an unbelievable win, my favourite I think.
"In terms of what we've had to deal with our position before the game and our position during the game, to find a way to beat a Fulham team who are in a really good moment.
"They're so strong depth-wise. They have like-for-like players on their bench, an unbelievable bench, and we're in a different moment. We can be as strong as that, but at this moment we're not."
Ahead of the games that will take place over the next two days, Wolves move into eighth position in the standings, one point adrift of West Ham United who have played one match fewer.
Wolves now have a three-week break before their next Premier League fixture, instead turning their attention to an FA Cup quarter-final against Coventry City on March 16.