The Brummie attempted to make the third defence of his welterweight crown early this morning in the main event of UFC 304 in Manchester.
His first meeting with the Palestinian-American three years ago ended in a No Contest due to an accidental eye poke.
Edwards was confident of laying the ghost of that fateful night in Las Vegas to rest with a brutal victory.
But Muhammad had other plans, scoring a sensational unanimous decision victory with his dogged and determined wrestling.
A crestfallen Edwards said in his post-fight inter as cited by Sports Central: "Nothing [was] surprising, my body just felt tired from round one. "All week we've been feeling tired. But congrats to Belal. We'll get it back again."
Chants of “Headshot dead'” immediately rang throughout the arena as the fight got underway.
And it wasn’t long before Muhammad shot for a big takedown, which he secured.
He wasn't, however, able to keep Edwards on the ground for long as the champ got back to his feet and ended up reversing him in the clinch.
A stiff one-two down the pipe drew a big reaction from the crowd, as did the champ’s ensuing body kick.
But he soon found himself back on the canvas, where he remained for the remainder of the stanza.
Muhammad came out aggressive again after the restart, putting the Brummie under yet more relentless pressure.
And he secured yet another big takedown thanks to a single leg that sent his travelling supporters wild.
Edwards briefly got back to his feet but soon found himself hoisted up in the air again before being put back down on the canvas.
He managed to work his way back to his feet but was once again rag-dolled to the canvas.
The Team Renegade ace eventually managed to reverse the position and momentarily took the back before the end of the round.
Edwards opened up the third with low and high kicks but the latter didn't find its home.
And not long after that, Muhammad once again successfully shot for another takedown.
Edwards managed to scramble to his feet and took the back of the challenger.
He threatened for a rear-naked choke before the end of the stanza but Muhammad defended well until the horn.
Edwards landed a big stiff left hand flush shortly after the restart but the challenger took it well.
Muhammad responded a few moments later with a big straight right that somewhat silenced the crowd before shooting for yet another takedown.
And his success with the grappling continued as he got Edwards back to the ground and kept him pinned with a body lock.
Edwards battled valiantly on the canvas and managed to roll into full guard before partially taking the back before the horn.
Edwards started the fifth and final stanza with a sense of urgency and looked to land the head kick he KO’d Kamaru Usman with just over two years ago.
Muhammad shot for another takedown soon after but it was expertly stuffed.
But he eventually took the back thanks to some beautiful chain wrestling.
Muhammad was relentless after securing the body lock, throwing short and annoying punches to further frustrate the champion.
Edwards managed to secure a big reversal with less than a minute to go and bloodied up Muhammad with a huge elbow.
But his follow strikes proved to be academic as the horn sounded a few moments later and brought about the end of his reign as the king of the welterweights.
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