After miraculously recovering, he snubbed a warm-up and instead beat Garcia, 34, on points which earned him a super-fight with Manny Pacquiao.
But disaster struck once more as Spence suffered a retina injury in sparring and forfeited a potentially career-defining night.
The unbeaten American underwent successful surgery and for the second time avoided an early and enforced retirement.
But Ugas, 35, would instead replace him and beat Pacquiao, 43, sending the Filipino icon into retirement.
And ahead of their title fight this Saturday live on Showtime PPV, for different reasons it leaves both knowing the opportunity is there to be taken.
Spence said: “You never know what can happen, anything can happen.
“It’s about taking these opportunities by the ear, just like Ugas, he took the opportunity when he was offered the Pacquiao fight.
“He jumped on it and he made good of the opportunity. It’s just like me man, I get this opportunity with Ugas to seize another belt, I’m definitely going to take it.
“I’m not willing to take any tune-up fight with somebody that’s not at the top of the welterweight division.”
Ugas has been a largely avoided figure in the 147lb division, with his upset over Pacquiao proving why.
That night he came in with nothing to lose and became a star overnight – but this time he does bring something to the table.
Spence said: “Well, he’s definitely got something to lose – his belt. But I have a lot to lose too, I have two belts, he’s only got one.
“I feel like he’s very tough, very skilled, he comes from that old-school Cuban boxing background where they teach him all the fundamentals.
“He’s a guy that’s no pushover and that I can’t take lightly. He’s coming to get my titles.
“Especially with my goals which is to fight twice and hopefully become undisputed at the welterweight division.”
A win for Spence will not only put him one step close to the four-belt undisputed throne but also within touching distance of his dream fight.
WBO champ Terence Crawford, 34, who joins the Spence on the pound-for-pound rankings, is waiting in the wings.
He recently left Bob Arum’s Top Rank stable to test free agency.
And having taken out the welterweight competition alongside his fellow undefeated rival, the stage for them to fight has never been greater.
Spence said: “I think it can definitely happen, it’s a huge possibility.
“He don’t have any dancing partners at 147 that makes sense for him. So I think it can definitely happen.
“I feel like it will be at it’s biggest level, especially with me beating Ugas.
.css-bq4915{margin:0;padding:0;color:rgba(34,97,108,1);text-transform:uppercase;-webkit-text-decoration:none;text-decoration:none;font-family:The Sun;font-size:18px;line-height:1.333;font-weight:700;letter-spacing:0%;font-stretch:normal;display:inline;}.css-bq4915:hover:not(:disabled){-webkit-text-decoration:none;text-decoration:none;}‘WE WILL GO ON’ .css-8h3gc3{margin:0;padding:0;color:rgba(34,37,38,1);-webkit-text-decoration:none;text-decoration:none;font-family:The Sun;font-size:18px;line-height:1.333;font-weight:700;letter-spacing:0%;font-stretch:normal;display:inline;}.css-8h3gc3:hover:not(:disabled){-webkit-text-decoration:none;text-decoration:none;}
Ukrainian’s inspiring vid to family in US that ‘victory will soon be ours’
“Fighting for four belts is at the highest level, but for me I’ve got to get past Ugas.
“I have to get past him because if I don’t get past him, then it doesn’t happen.”