Major General Abulaziz al-Shalal appeared in a video aired on Al Arabiya TV to say that he was leaving the "regime army" to join the "people's revolution".
Dozens of generals have defected since the Syrian uprising began in March 2011. In July, Brig. Gen. Manaf Tlass was the first member of Mr Assad's inner circle to break ranks and join the opposition.
However, Maj. Gen Shalal is one of the most senior and as the leader of the security branch charged with punishing disciplinary failures within the Syrian army, his decision is particularly embarrassing for the Syrian president.
"I, General Abdel Aziz Jassem al-Shalal, commander of Syrian military police, announce that I am defecting from the regime army, to join the people's revolution," the officer said in his video.
"The army has deviated from its essential mission, which is to protect the country, and it has morphed into murderous, destructive gangs."
The officer added that "the destruction of cities and villages, and the commission of massacres against our people, defenceless civilians, who took to the streets calling for freedom" had prompted him to defect.
It was unclear on Wednesday precisely where Maj. Gen Shalal had fled to. Some opposition sources said that he was smuggled across the border into Turkey in nighttime operation that lasted several hours.
The military police's role in Syria is to punish soldiers that have committed an offence whilst serving in the army, and to track down and arrest reservists that have failed to show up when called for the compulsory military draft.
"The main job of the military police was to raid houses and search for reservists and force them into the army," Dr Mousab Azzawi from the opposition Syrian Network for Human Rights said.
A Syrian security source confirmed Maj. Gen Shalal's defection to Reuters but played down its significance.
"Shalal did defect but he was due to retire in a month and he only defected to play hero," the source said.
Thousands of Syrian soldiers have joined the rebel opposition or just fled the country over the passed year, though the numbers and profile of the defectors has not yet reached a critical mass to topple the regime and most of the complex infrastructure of the government's multiple security and intelligence branches remains in place.
News of the defection came as the opposition watchdog the Syrian Observatory for Human Rights said that 20 people, including eight children, where killed in a government shelling attack in an agricultural area of Raqqa province in the north of the country.
Amateur footage showed a row of a dozen corpses, including those of children lain out in a room. Blood splattered some of the victims' clothes and yells of despair could be heard in the background.
There were further signals yesterday that the regime was coming under heavy pressure. Syrian foreign ministry officials headed to Moscow amid reports of a US-Russian initiative for a transition in Syria.
Formerly a dependable international ally of President Assad, Russian President Vladimir Putin last week distanced himself from the regime by recognising that a "change [in leadership] is certainly on the agenda".
The talks are expected to also discuss proposals for ending Syria's 21-month-old crisis that have been apparently made by international envoy Lakhdar Brahimi during his current visit to Damascus. Mr Brahimi is to Moscow on Saturday, Russia's Deputy Foreign Minister Mikhail Bogdanov told ITAR-TASS on Wednesday.
The make up of the proposal is as yet unclear. Earlier in December, Mr Brahimi held tripartite meetings between Russia and the United States. His previous, failed proposal, centred on a transitional government that left open Assad's future role, which was deemed unacceptable by the opposition.
The diplomatic development came on a day when the war in Syria reached a new and grim death count of more 45,000 people according to the Syrian Observatory.