City suffered a blow before kick-off with the news that Peter Whittingham was unfit. Ross McCormack slotted into a wide berth and Darcy Blake took up a central midfield role alongside Gavin Rae.
Former City players Willo Flood and Gary O'Neil were in the visitors starting line-up along with former Wales international keeper Danny Coyne.
City made a superb start after winning a corner in the opening minute. The ball went out to Blake and his centre was met by Gabor Gyepes, who prodded the ball goalwards for Bothroyd to stab home from close range.
Blake and Rae were working hard and winning the early midfield battle and the Boro goal came under pressure from both Michael Chopra and McCormack, with City using the flanks to good effect.
Jeremie Aliadiere had a fleeting chance on the half hour after the Bluebirds failed to clear but Anthony Gerrard slid in to tackle and his shot flew high over the bar.
Five minutes before the break, Bothroyd went close after neat play from Adam Matthews and Chopra.
City should have had a penalty in the 45th minute when Chris Burke was brought down by O'Neil but referee Darren Deadman deemed otherwise and booked Burke for diving.
The visitors should have levelled four minutes after the break when a cross by Andrew Taylor was met at the near post by Leroy Lita but his header went well wide.
The visitors had the ball in the net on the hour through Lita but the goal was disallowed and both Lita and Boro skipper Barry Robson were booked for protesting too much.
Lita was looking dangerous up front alongside sub Chris Killen and the City defence needed to be at their best to stay ahead as Boro went looking for an equaliser.
Robson forced a brilliant one-handed save from David Marshall after the ball had bobbed about City's danger area but the Bluebirds were hanging on to their lead despite mounting pressure.
Marshall was again in the action in the 80th minute after tipping over a close-range header from Killen and then he palmed over an O'Neil free-kick as the game entered the final five minutes.
There was time for Blake to hit the crossbar in time added on as the City held out for a well-deserved victory and the double over their visitors.