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A launch window opens at 6:30 pm (2330 GMT) from the company's Starbase facility near a southern Texas village that recently voted to become a city, also called Starbase.
Standing 403 feet (123 meters) tall, Starship is the largest and most powerful launch vehicle ever built, and it carries Musk's hopes of making humanity a multi-planetary species.
NASA is also counting on a variant of Starship to serve as the crew lander for Artemis 3, the mission to return Americans to the Moon.
But the last two tests ended with the upper stages erupting into fiery cascades that sent debris raining down over Caribbean islands and disrupting flights -- piling more pressure onto SpaceX to get it right this time.
The company is betting that its aggressive testing approach, which helped it become the dominant force in commercial spaceflight, will once again pay off.
Still, it acknowledged in a statement that progress "won't always come in leaps."
According to the Wall Street Journal, SpaceX is shifting personnel and resources to the Starship program in a push to have the vehicle ready for a Mars mission as soon as next year.