The National League for Democracy (NLD) party head will run in Kawhmu, southwest ofRangoon, in polls on 1 April.
Ms Suu Kyi was released from house arrest in November 2010.
Her party boycotted the last elections but has now rejoined the political process amid reform inBurma.
The by-election will fill 48 parliamentary seats left vacant when cabinet members assumed their ministerial posts.
The NLD plans to contest more than 40 seats in the event that is being seen as a key test of the military-backed government’s reformist credentials, says BBC South East Asia correspondent Rachel Harvey.
Ms Suu Kyi is seeking office in the sleepy, ruraltownshipofKawhmu. It was one of the areas hit hard by Cyclone Nargis, which left at least 138,000 people dead in theRangoonregion and Irrawaddy Delta in 2008.
She made no public statement as she filed registration papers but as she left the office she was mobbed by hundreds of supporters during an impromptu walkabout.
This is the first time that Ms Suu Kyi will participate in an election. She was under house arrest in 1990 when her party, the National League for Democracy (NLD), won the election by a landslide. It was not allowed to take power.
The NLD boycotted the 2010 election that saw the military-backed civilian administration of President Thein Sein replace the military junta.
The new administration has since entered into dialogue with Ms Suu Kyi and changed the electoral laws that led the NLD to boycott the 2010 polls.
Last week the government signed a ceasefire deal with Karen rebels – who have fought for greater autonomy for more than 60 years.
It also released many political prisoners on 13 January, includingBurma’s most prominent political dissidents – 88 Generation Student leaders Min Ko Naing and Ko Jimmy, as well as Buddhist monk Shin Gambira.
TheUShas described the release of political prisoners as a substantial step towards democratic reform and says it will start the process of exchanging ambassadors withBurma.
Burmaremains the subject of economic sanctions from the European Union, theUnited StatesandCanada, among others. Of the major economies, onlyChina,IndiaandSouth Koreahave invested in the country.
But Western leaders have said they will match progress towards democracy inBurmawith concessions and political incentives.
The Philippines- one of the most outspoken critics in Asia of Burma’s military rule – has also reiterated its call for the lifting of sanctions onBurma, citing “unprecedented political and economic reforms” towards democracy.
Both countries are members of the Association of South East Asian Nations, whichBurmawill chair in 2014.