Senators voted 31-17 to pass the bill, moments after the Mississippi House of Representatives rejected the same bill 54-60.
Mississippi is one of six states without a lottery, and Republican Gov. Phil Bryant has been pushing lawmakers to legalise lotteries for more than one year.
Bryant wants the extra funds to be used to help maintain roads and bridges, as many bridges in the Magnolia state are closed for structural reasons.
The bill failed to move out of the House after the number of Democrats supporting it fell from 36 on Friday to 18 on Monday. The Senate and House last week passed different versions of a lottery bill, and the House and Senate must agree on a single version before it can be handed to the governor.
One of the potential reasons for the sharp decline was the removal of a provision which would allow video lottery terminals in locations such as truck stops and service stations, after opposition from casinos and religious groups.
This is because both groups are keen to limit where legal gambling can take place in the state to casinos situated on the Mississippi River and Gulf Coast.
The bill was held for the possibility of more debate, which gives legislators and supporters a chance to revise the bill in an attempt to pass it through the House.
