The Tesla and SpaceX entrepreneur was pushed into the top slot after Tesla’s share price increased on Thursday.
He takes the top spot from Amazon founder Jeff Bezos, who had held it since 2017.
Mr Musk’s electric car company Tesla has surged in value this year, and hit a market value of $700bn (£516bn) for the first time on Wednesday.
That makes the car company worth more than Toyota, Volkswagen, Hyundai, GM and Ford combined.
Mr Musk reacted to the news in signature style, replying to a Twitter user sharing the news with the remark “how strange”.
An older tweet pinned to the top of his feed offered further insight into his thoughts on personal wealth.
“About half my money is intended to help problems on Earth, and half to help establish a self-sustaining city on Mars to ensure continuation of life (of all species) in case Earth gets hit by a meteor like the dinosaurs or WW3 happens and we destroy ourselves,” it reads.
The tycoon’s fortunes have been buoyed by politics in the US, where the Democrats will have control of the US Senate in the forthcoming session.
Daniel Ives, an analyst with Wedbush Securities wrote: “A Blue Senate is very bullish and a potential ‘game changer’ for Tesla and the overall electric vehicle sector, with a more green-driven agenda now certainly in the cards for the next few years.”
Expected electric vehicle tax credits would benefit Tesla, “which continues to have an iron grip on the market today”, he added.
Mr Bezos has also seen his fortunes rise over the past year. The coronavirus pandemic has meant Amazon benefited from stronger demand for both its online store and cloud computing services.
However, he gave a 4% stake in the business to his ex-wife MacKenzie Scott after they split, which helped Mr Musk overtake him.
In addition, the threat of regulation has meant Amazon’s stock has not risen as high as it might otherwise have done.