Umar Naseer, who was in charge of police and was effectively Yameen's deputy, submitted his resignation to the president's office on Tuesday night.
"I thank HEP (his excellency president) Yameen and others for all their support," Naseer said, announcing his resignation on Twitter.
Observers say Naseer had recently fallen out with Yameen and he becomes the 11th minister to resign or be sacked since the hardline president came to power at a controversial election in 2013.
The Maldives has been rocked by political turmoil in recent years, with almost all of Yameen's key rivals jailed or exiled from the popular honeymoon destination.
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The resignation comes weeks after Mohamed Nasheed, the country's first democratically elected leader, was granted asylum in Britain.
Nasheed was sentenced to 13 years in prison on controversial terrorism charges last year but was allowed to travel to Britain for surgery in January and granted political asylum in May.
That position had been vacant since the arrest in November of incumbent Ahmed Adeeb.
Adeeb was jailed for 15 years last month for plotting to kill Yameen by allegedly setting off a bomb on his speedboat last September that did not harm the president.
Opposition activists say dissidents risk arrest or exile under Yameen, the half brother of former strongman Maumoon Abdul Gayoom, who ruled the archipelago for 30 straight years until he was defeated in the first democratic election in 2008.