After Russian Foreign Minister Sergey Lavrov had presented the treaty and urged lawmakers to accept the region as a part of the Russian Federation, the document was approved on a vote of 443 to 1.
Russia's Federation Council upper house will hold a similar vote Friday, completing ratification of a treaty that was signed by President Vladimir Putin on Tuesday.
Speaking "on behalf" of Putin, Lavrov had told the State Duma that folding Crimea into Russia was needed to protect ethnic Russians there.
"I am certain that passing the document will become a turning point in the destiny of multi-ethnic nations of Crimea and Russia, who are related with close ties of the historical unity," Lavrov said.
"These nations joining in the framework of one state will certainly help grow wealth and prosperity and is in line with Russia's interests."
Russia's moves to annex the Black Sea peninsula have turned a confrontation with Europe and the United States into the biggest crisis in East-West relations since the Cold War.
Approval of the treaty in the State Duma was in no doubt as Russia has stood defiant despite Western leaders denouncing Moscow's actions as a violation of Ukraine's sovereignty and a breach of international law.
European Union leaders are due to meet in Brussels, Belgium, on Thursday to discuss the crisis, with possible further targeted sanctions.
U.S. and EU officials have imposed sanctions on more than two dozen Russian and Crimean officials, and urged Russia to avoid escalating the crisis. Moscow has ignored those calls.
U.S. President Barack Obama on Thursday announced more sanctions on people and one bank in response to Russia's annexation moves as well as a new executive order that authorizes possible further sanctions on what he called "key sectors" of the Russian economy.
"We want the Ukrainian people to determine their own destiny and have good relations with the United States, Russia, Europe -- anyone they choose," he said in calling for continued diplomatic efforts.
The new U.S. sanctions target 20 officials, including senior Russians and "cronies" who hold significant influence in the Russian system, as well as one bank that holds "significant" resources, a senior U.S. administration official told reporters.
British Prime Minister David Cameron told reporters at the EU Heads of State summit there would likely be more asset freezes and travel bans.
Lavrov told lawmakers that sanctions "have never brought any positive results" and that there were no grounds for them.