Two days after a loss against Adelaide, the Heat lost 10 for 36 on Sunday night to be dismissed for 120, chasing 165.
After the Renegades made 6-164, the Heat made a blistering start with Sam Heazlett and Chris Lynn belting an 84-run opening partnership in six overs.
Lynn's innings included a 24-run over off Mohammad Nabi featuring three sixes including a 110m monster hit.
But when the Heat captain fell for 41 off 15, the rot set in.
South African star AB de Villiers was bowled for two by legspinner Cameron Boyce, who ended the match with 4-15 in a man-of-the-match display.
Boyce removed Matt Renshaw with his next ball and, suddenly, the Heat had lost three wickets for two runs.
Heazlett and Joe Burns set about steadying the ship but, when Heazlett fell for 56, an even bigger collapse was sparked.
English spinner Samit Patel (2-22) dismissed Jimmy Peirson for a second golden duck of the innings, before Burns (14) was run out in a disastrous mix-up involving Ben Cutting.
From there, the Heat's innings wrapped up quickly and the Renegades charged to their second win of the season.
The Heat's next home game against the Sixers on Thursday evening will be crucial in their battle to the finals.