Gavin, twin brother of world champion Jamie, beat Jorge Sanchez in a WBC Silver super bantamweight title and eliminator match, at Manchester Arena.
It takes his record to W15 L 0 D2 since turning professional five years ago.
The 29-year-old European champion defeated previously unbeaten Sanchez, 25, from Panama City.
Sanchez, nicknamed El Bufalo was predicted to be the most dangerous early on and he was a busy blur, in his pink shorts, in the first round.
But in the second, he was caught out.
McDonnell had defended comprehensively but then suddenly landed with a short right hand to the chin, sending Sanchez to the canvas with 25 seconds to go of the round.
The Panamanian slugger was full of beans, though, and seemed to hurt the Doncaster man in the next round with a right hand. But the Dave Coldwell fighter shrugged it off and contained the visitors' attack.
McDonnell, boxing sensibly and conservatively on the back foot, kept rocking his rival with the jab and the occasional combination.
Sanchez needed to make some significant contact, but was struggling to be precise against the taller man, who kept clocking up round wins.
Despite animated brother Jamie jumping up and down in frantic support ringside, there seemed little to worry about in the final rounds.
Super-fit Gavin eased to a points win.
Afterwards, Gavin said he'd put in a good performance, as his opponent had a "bit of a dig."
He said he would not be out-done in the battle of brothers to gain the best belts.
Jamie said he was "chuffed to bits" with his elder twin.
*The South Yorkshireman was chief support to the Carl Frampton v Scott Quigg super bantamweight TV blockbuster, which attracted Sheffield world champion Kell Brook and former city superstar Naseem Hamed into the crowd.
Frampton won the 12-rounder on a split decision in a battle which seemed to take ages to warm up.