The 36-year-old's grappling prowess proved too much for the previously undefeated champion, securing a unanimous decision victory.
The win marked a dramatic reversal of fortunes for Muhammad, whose 2021 fight with Edwards was declared a no-contest due to an accidental eye poke.
The early morning start time, designed to cater to a US audience, seemed to impact 32-year-old Edwards, who admitted to feeling "tired" post-fight.
The 5:30 BST start time had been a subject of much discussion, with fighters adjusting their training schedules to accommodate the unusual hours.
"Not surprising, my body just felt tired from round one," said Edwards.
"All week I've felt tired. Congratulations to Belal, we will be back."
The main event was preceded by a first-round TKO by interim UFC heavyweight champion Nathan Aspinall against Curtis Blaydes, as well as a thrilling victory for Paddy Pimblett, who ignited the crowd with a first-round submission.
However, the night ultimately belonged to Muhammad, who silenced the home crowd with his impressive performance in the main event to extend his winning streak to 10 in a row.
