The Venoms headed into the fixture at Fufa Technical Centre in Njeru looking for their second win having drawn their opener and won the second one.
Meanwhile, Busoga came into the match without a win, having lost three matches and drawn one.
They also had financial problems that had affected the team’s training sessions heading into the fixture.
Geoffrey Wasswa broke the deadlock for Vipers with a brilliant free-kick in the 17th minute.
However, Busoga pulled level courtesy of George Kasonko in the 25th minute.
Their goal was short-lived as Milton Karisa made it 2-1 for Vipers this time.
He headed home from a corner in the 27th minute and the game went into half-time standing at 2-1 in favour of the champions.
Vipers continued to attack Busoga on resumption and it was no surprise when Karim Watambala made it 3-1.
He found the bottom corner with a brilliant strong effort.
Busoga were not done yet as they pulled a goal back in the 56th minute courtesy of Ismail Mugulusi.
Paul Mucureezi then curled the ball into the back of the net from a free-kick after Bobosi Byaruhanga was fouled.
Mucureezi then made it 5-2 for Vipers in the 84th minute but three minutes later Paul Ssekulima scored another one for Busoga.
However, it was not enough as Vipers ran away 5-3 winners.
Vipers has now moved to the eighth position with seven points from three games while Busoga United remain 15th with one point.