Argyle captain Karl Duguid's classy finish on the half-hour mark was added to by Luke Summerfield's 72nd-minute penalty after Hornets captain Jay DeMerit had inexplicably handled.
John-Joe O'Toole scored a late goal for the third home game in a row but it was not enough for Boothroyd's side.
And after seeing both striker Tamas Priskin and right-back Lloyd Doyley carried off with hamstring injuries, Boothroyd admitted that his threadbare squad is stretched beyond its limits.
He said: "If you were to say we are in for a long, hard winter I would have to get my coat and agree with you.
"We've got one recognised centre-forward at the club.
"With our best 11 players on the pitch we'll go toe-to-toe with anyone but to lose two players with hamstring injuries is a massive blow.
"Plymouth made seven changes but if I made seven changes I would have had the physio at right-back.
"I'm going to have a chat with the chairman and see what's available because it's a lot to ask for this squad to play as many games as we have got coming up."
Argyle climbed off the foot of the Coca-Cola Championship table with the three points but Boothroyd believed his side gave their all.
He said: "I asked for a response to Saturday and in terms of effort and energy levels we were Champions League.
"But in terms of end product we were a long way from the Champions League."
Plymouth boss Paul Sturrock claimed that his radical overhaul of the side paid off after a win based on graft.
Sturrock made seven changes from the team which was beaten 2-1 at home to Norwich on Saturday to cap their worst start in 14 years.
And after seeing his second-string grind out a win, the Scot challenged those he had left out to double their efforts.
He said: "We went with a squad of players at the start of the season and a lot of them were making their first starts of the season here, and they merited their selection.
"I went for an honest, hard-working team tonight and that's what we needed.
"Some of the more technically-gifted players have got to learn that in this league, work-rate comes first.
"I might have been too cavalier at the start of the season and that cost us but now we might have to come away from home and set our stall out.
"But we are not in any way out of the mire. This is going to be an uphill tussle all season.
"We have got to realise that we are fighting for our lives in this division between now and the end of the season.
"There will be a lot of nights like this between now and May."
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