Dimitar Berbatov set Fulham on their way with an earlier opener from what appeared to be an offside position, only for Kevin Nolan to equalise three minutes into the second half.
Hugo Rodallega restored the hosts' lead and an own goal by Joey O'Brien sealed only their second win of 2013, to lift them above their opponents and back into mid-table.
The Hammers are just seven points clear of the relegation zone in 13th and are winless in four league matches and six games in all competitions now.
"We were disappointed that we're not putting the chances away at the minute," McDonald told Sky Sports.
"That seems to be costing us as well as refereeing decisions. Their first goal wasn't just one person standing in an offside position, but three of them, so it's hard to take.
"We came out in the second half and forced the issue. We put Fulham on the back foot and we're pleased with lots of aspects of our play but disappointed that we conceded another three goals.
"Form the start of the season, if we're in this position, then I'd say we would be very, very happy. If we keep on playing the way we are playing and we tighten up, then I'm sure we'll be fine and the form will turn around."
McDonald was pleased with the introduction of Andy Carroll as he made his first appearance in 11 matches. He added: "We created some good chances and felt we should have two penalties in the second half."