Cathal McShane suffered a serious looking ankle injury in 13-man Tyrone's 2-25 to 0-12 loss in Galway as Monaghan beat Mayo 2-16 to 0-13 in Division One.
A dominant Galway were 0-13 to 0-6 ahead when McShane - who recently turned down an AFL contract offer - was injured early in the second half.
Tyrone fought back to trail by only three but Shane Walsh's penalty and Paul Conroy's goal ended the contest.
Red Hand duo Kieran McGeary and Frank Burns were sent off.
McGeary was red carded late in the first half for a high challenge on Eamonn Brannigan when Tyrone trailed 0-9 to 0-4 with a frustrated Burns sent off shortly after Walsh's penalty snuffed out any Red Hand hopes of an unlikely comeback.
McShane's ankle 'at least disclocated' - Harte
Tyrone were already in big trouble when McShane sustained his injury with Niall Morgan's sortie upfield to have an attempt at goal summing up their first half as his effort went way wide.
Manager Mickey Harte said afterwards that McShane's ankle "is at least dislocated" although he added that the full extent of the damage remains unclear.
"It's pretty serious. The doctor says it's definitely a bad injury," Harte told TG 4's GAABEO.
"It's just so unfortunate because he made such an effort to decide to stay at home with us. And now he's gone for God knows how long."
The result was the biggest defeat Tyrone have suffered since Harte's appointment in late 2002.
With Walsh tormenting Ronan McNamee, Galway responded to Darren McCurry's opening point to move into a 0-3 to 0-1 lead and the advantage became 0-8 to 0-3 as impressive Corofin midfielder Ronan Steede hit his second point and Damien Comer and Adrian Varley were also among the scorers.
McShane had started well for Tyrone as he kicked their third point but Galway quickly began to curb his effectiveness as the Red Hands appeared to have no attacking options beyond hitting high balls into the full-forward.
Colm Cavanagh did have a great goal chance when 0-6 to 0-3 down with Galway keeper Conor Gleeson making a fine double save to deny the Moy man.
Tyrone's prospects weren't helped by McGeary's 29th-minute red card with his attempt to shoulder Brannigan mistimed as the Galway man was caught high.
After leading 0-12 to 0-6 at the break, Walsh's fourth point extended Galway's advantage before the long interruption following McShane's injury as he appeared to land awkwardly on his ankle after winning possession nearly halfway.
The Red Hands rallied to cut Galway's lead to three - helped by four successive McCurry points.
However any prospect of a Red Hand comeback was ended as the lively Comer earned a penalty following a hand trip by Liam Rafferty, with Walsh blasting the penalty down the middle of the goal as Morgan dived to his left.
Substitute Paul Conroy added Galway's second goal after Burns' dismissal.
Down to the 13 men, Tyrone's challenge completely subsided in the closing stages as Galway added a succession of late points.
The defeat leaves Tyrone on four points from as many games and far from safety in Division One with their next game at home to All-Ireland champions and Division One leaders Dublin next weekend.
Monaghan punish Mayo indiscipline at Clones
Monaghan took a huge step towards maintaining their Division One status as they earned a merited eight-point victory over an ill-disciplined Mayo outfit.
The Farney led by only two two after 62 minutes but they outscored James Horan's side 1-5 to 0-1 during the remaining action after Jordan Flynn's red card.
The first-half exchanges were competitive as Monaghan fought back from 0-2 to 0-0 down to level at 0-3 to 0-3 after 15 minutes.
Points from James Durcan and Oisin Mullin helped Mayo move two ahead again only for Conor McCarthy's 24th-minute goal to put the home side ahead as he ran past three defenders.
After a trademark Rory Beggan free, Mayo were on terms again by the break following points from Darren Coen and Diarmuid O'Connor.
As Monaghan stepped up the pace, they moved into a three-point advantage by the 53rd minute.
The game still remained in the melting point before Flynn's 62nd-minute red card and within a minute, Mayo's challenge had evaporated as Kieran Duffy fired in Monaghan's second goal with the home side adding five further points to run out comfortable winners.
ALLIANZ FOOTBALL LEAGUE RESULTS